Journal of Dermatological Treatment
ISSN: 0954-6634 (Print) 1471-1753 (Online) Journal homepage: http://www.tandfonline.com/loi/ijdt20
Serum irisin levels in patients with psoriasis Anna Baran, Hanna Myśliwiec, Paulina Kiluk, Magdalena Świderska & Iwona Flisiak To cite this article: Anna Baran, Hanna Myśliwiec, Paulina Kiluk, Magdalena Świderska & Iwona Flisiak (2017) Serum irisin levels in patients with psoriasis, Journal of Dermatological Treatment, 28:4, 304-308, DOI: 10.1080/09546634.2016.1254327 To link to this article: http://dx.doi.org/10.1080/09546634.2016.1254327
Accepted author version posted online: 27 Oct 2016. Published online: 10 Nov 2016. Submit your article to this journal
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Date: 22 September 2017, At: 08:20
JOURNAL OF DERMATOLOGICAL TREATMENT, 2017 VOL. 28, NO. 4, 304–308 http://dx.doi.org/10.1080/09546634.2016.1254327
ORIGINAL ARTICLE
Serum irisin levels in patients with psoriasis Anna Barana, Hanna Mysliwieca, Paulina Kiluka, Magdalena Swiderskab and Iwona Flisiaka
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a Department of Dermatology and Venereology, Medical University of Bialystok, Bialystok, Poland; bDepartment of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland
ABSTRACT
ARTICLE HISTORY
Background: Irisin has been proposed to regulate metabolic diseases such as obesity, diabetes or metabolic syndrome which are common comorbidities in psoriasis. Objectives: The aim of this study was to evaluate the serum irisin level in psoriasis and elucidate possible associations with disease activity, inflammatory or metabolic parameters and topical treatment. Methods: Thirty-seven individuals with active plaque-type psoriasis and 15 healthy controls were enrolled. Blood samples were collected before and after two weeks of therapy. Serum irisin concentrations were examined by enzyme-linked immunosorbent assay (ELISA). The results were correlated with psoriasis area and severity index (PASI), body mass index (BMI), inflammatory and biochemical markers, lipid profile and effectiveness of topical treatment. Results: Irisin serum levels were insignificantly increased in psoriatic patients in comparison to the controls (p ¼ 0.38). No significant correlations between investigated adipokine and several indicators of metabolic disorders, nor BMI (p ¼ 0.37) or PASI (p ¼ 0.5) were found. Significant positive correlations with C-reactive protein (CRP) (0.009), lipocalin-2 (p ¼ 0.02), age (p ¼ 0.02) and disease duration (p ¼ 0.008) were noted. After topical treatment, serum irisin level did not significantly change (p ¼ 0.31), despite clinical improvement. Conclusions: Irisin might be a marker of inflammation in psoriatic patients, but may not be a reliable indicator of metabolic conditions, severity of psoriasis nor efficacy of antipsoriatic treatment.
Received 3 August 2016 Accepted 23 October 2016 Published online 11 November 2016
Introduction Psoriasis is a common chronic inflammatory disease, affecting over 2% of the population worldwide. Patients with psoriasis are at higher risk of numerous comorbidities such as obesity, cardiovascular disease (CVD), metabolic syndrome (MS) or insulin resistance (IR) and diabetes mellitus (DM) (1,2). Therefore, currently this dermatosis has been considered as a systemic disorder with impact on psoriatics’ morbidity and mortality. Psoriasis shortens patients’ life by an average of 5–7 years compared with general population due to increased risk of myocardial infarction and thromboembolic events (3). There is a significantly higher prevalence of metabolic syndrome in psoriatic patients ranging from 40% to 65% (4). Interesting, but very complex, is association between psoriasis and obesity, as one of the pivotal components of MS. Adipose tissue is not only an energy reservoir but primarily has metabolic, endocrine and immunomodulatory functions. Psoriatic patients have more than twice higher risk of obesity. On the other hand, obesity often precedes the development of psoriasis and body mass index (BMI) correlates with the risk of this dermatosis. Common genetic background, chronic systemic inflammation and increased synthesis of proinflammatory cytokines or insulin resistance promote endothelial dysfunction and atherosclerosis consequently causing cardiac insufficiency in patients with psoriasis (4,5). Strong relations of psoriasis with numerous metabolic disorders have been leading to investigate potential role of various adipokines or other newer and newer proteins in psoriasis. CONTACT Anna Baran Poland
[email protected]
KEYWORDS
Psoriasis; irisin; myokine; obesity; anthralin
Beside adipose tissue, muscle tissue has been recently identified as an active endocrine organ that also regulates metabolism (6). Irisin, a 12k Da novel myokine comprised of 112 amino acids, €m et al. 2012 (7). was isolated from muscle tissue by Bostro Overexpression of peroxisome proliferator-activated receptor-c coactivator 1a (PGC1a) in skeletal muscle during exercise stimulates cleavage of the membrane protein fibronectin type III domain 5 (FNDC5) which is the precursor of irisin (6,8). This myokine is involved in converting white adipose tissue to brown adipose tissue which increases thermogenesis and may improve systemic metabolism or insulin sensitivity (5,9,10). Irisin is synthesized generally in skeletal muscle, but is also distributed in cardiac muscle, adipose tissue, liver, brain, bones, sebaceous glands, pancreas, kidney and others (4,10). It has been proved that irisin is not only a myokine but adipokine with its auto- and paracrine actions (10,11). It was assumed that irisin could be an indicator of body fat mass as it was elevated in obese subjects in many studies. However, it could be only a compensatory mechanism (10–12). Decreased serum irisin levels were reported to be linked with chronic kidney disease, nonalcoholic fatty liver disease and diabetes (8). Zhang et al. (13) suggested that irisin might be a marker for macrovascular disease in DM. In recent study on mice, the authors have demonstrated a protective effect of treatment with oral irisin on atherosclerosis (14). Irisin seems to be involved in lipid or glucose metabolism and most likely associated with IR, DM, CVD or MS which are common comorbidities in psoriasis (8,10,15). It was also suggested that irisin might play a role in
Department of Dermatology and Venereology, Medical University of Bialystok, 15-540 Bialystok, Zurawia 14 St,
ß 2016 Informa UK Limited, trading as Taylor & Francis Group
JOURNAL OF DERMATOLOGICAL TREATMENT
aging process, cognitive capacity or bone metabolism (8,10). Since the discovery of irisin numerous studies have been conducted to assess its role in different diseases. Promising results from other medical fields lead us to explore the novel adipokine in relation to psoriasis, the more there is no data on this topic. The aim of this study was to assess serum irisin levels in patients with plaque-type psoriasis and their relationship with the disease severity, inflammatory or metabolic parameters, other adipokines and topical treatment used.
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Materials and methods The study was conducted on 37 patients (15 females and 22 males) with flare of plaque-type psoriasis, with median age 49 (35–64) years, and 15 sex-, age- and BMI-matched healthy controls. Other types of psoriasis and any other chronic inflammatory or metabolic diseases, which might interfere with the evaluation of psoriasis, were exclusion criteria. None of the participants were under any dietary restriction, systemic nor topical treatment for one month prior to enrollment. BMI was evaluated as weight/ height2 (kg/m2). Psoriasis area and severity index (PASI) was recorded by the same investigator (A.B.) in all patients. The study group was divided depending on the severity – PASI score below 10 defined psoriasis as mild, between 10 and 20 as moderate and above 20 as severe. We divided also our patients into four groups depending on BMI, group 0 related to normal weight (BMI 18.5–24.9) and consisted of 10 persons, 1 – meant overweight (BMI 25–29.9) found in 15 psoriatics, 2 – obesity I grade (BMI 30–34.99) – 8 patients, group 3 – obesity II grade (BMI 35–39.9) included 4 patients. Blood samples were obtained before starting treatment and repeated after two weeks of application of 5% salicylic acid ointment and 0.3% anthralin. All participants gave their signed informed consent before participation and the study was approved by the Bioethical Committee of Medical University of Bialystok. Fasting blood samples were collected from the study and control group using vacutainer tubes and allowed to clot for 30 min before centrifugation for 15 min at 1000 g, then serum was divided for further measurements and stored at 80 C. Irisin serum levels were measured by enzyme-linked immunosorbent assay (ELISA) supplied by BioVendor (catalog no. RAG018R) with detection limit of 1 ng/ml and assay range: 0.001 lg/ml–5 lg/ml. The concentration was determined by interpolation from calibration curves prepared with standard samples provided by the manufacturer. Serum concentrations of other selected adipokines were measured using ELISA supplied by QuantikineV (R&D Systems, Minneapolis, MN) precisely described in our previously published studies. R
Statistical analysis Data analysis are described as mean ± standard deviation (±SD), median value, confidence interval (CI, 25–75% percentile) and percentage when appropriate. The Student’s T-test was used to compare the averages among groups. Correlations were performed using Mann–Whitney U test and the Spearman coefficient correlation for non-normal variables. The Chi-Square test was used for the analysis of qualitative data. Quantitative data divided in categories were ranked using one-way ANOVA Kruskal–Wallis test. Logistic regression was used for multivariate analysis of associations. Values of p < 0.05 were considered statistically significant. Statistical analyzes were conducted using the GraphPad Prism5.0 (La Jolla, CA) and Statistica 12.0 (Statsoft, Tulsa, OK).
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Results The study included 37 patients with active plaque-type psoriasis, 15 women and 22 men with the mean age of 48.6 ± 2.4 (19–84) and 15 age-, sex- and BMI-matched healthy volunteers. The duration of the disease ranged from 1 to 55 years with a mean of 17.4 ± 1.8 and the relapse duration ranged from 0.5 to 2 years with a mean of 4.4. ± 0.9. Median score of BMI was 27 kg/m2 (24–31). Basal PASI score ranged from 5.5 to 32.1 with a median score of 18.8 (10.7–21.8). The demographic, clinical and laboratory data of the study group are summarized in Table 1. Of the 37 patients studied, 7 persons (18.9%) had mild psoriasis (PASI 20). Significant statistical correlations between serum irisin level and age or disease duration were noted (Table 2). The median irisin serum levels in psoriatic patients were 8.23 (0.6–11.01) pg/ml and did not differ significantly (p ¼ 0.38) comparing to the controls, however, it was 2.5 times higher (Figure 1, Table 3). In patients with psoriasis, serum irisin level did not correlate with the PASI score (p ¼ 0.5) nor BMI (p ¼ 0.37) (Figure 2, Tables 2 and 3). Assessing irisin levels depending on the severity of psoriasis in each group of patients, no statistical correlations in comparison to the controls were noted (Table 4). There were no significant relations between the study and control group in terms of liver enzymes activity, glucose nor lipids levels (p > 0.05) (Table 2). There were no significant differences between the groups depending on BMI comparing to the healthy subjects (Figure 3). Table 1. Selected characteristics of the patients. Characteristics SR [mm/h] CRP [mg/l] WBC [103/ml] PLT [103/ml] Glucose level BMI (kg/m2) PASI before treatment PASI after treatment
Median (CI) 16 (7–36) 3.4 (2.1–15.6) 7.3 (6.3–8.7) 203 (164–265) 89 (7–94) 27 (24–31) 18.8 (10.7–21.8) 8.4 (4.7–12.3)
Table 2. Main variables of the study in patients before and after treatment and correlations with serum irisin levels.
Characteristics SR [mm/h] WBC [103/ml] ALT [IU/l] AST [IU/l] PLT [x103/ml] BMI [kg/m2] RBC [x103/ml] Glucose level [mg/dl] CRP [mg/l] Cholesterol [mg/dl] HDL-C [mg/dl] LDL-C [mg/dl] TG [mg/dl] Adiponectin Leptin RBP-4 Lipocalin H-FABP A-FABP YKL-40 Age [years] Relapse duration [months] Disease duration [years] a
Serum irisin before treatment r (p values)
Serum irisin after treatment r (p values)
0.35 (0.03a) 0.05 (0.77) 0.15 (0.38) 0.04 (0.82) 0.05 (0.78) 0.15 (0.37) 0.09 (0.59) 0.18 (0.27) 0.25 (0.13) 0.16 (0.54) 0.06 (0.83) 0.45 (0.07) 0.054 (0.84) 0.04 (0.79) 0.02 (0.91) 0.03 (0.82) 0.37 (0.02a) 0.10 (0.54) 0.23 (0.16) 0.08 (0.63) 0.39 (0.02a) 0.03 (0.83) 0.43 (0.008a)
0.21 (0.21) 0.001 (0.99) 0.0005 (0.99) 0.02 (0.88) 0.001 (0.99) 0.27 (0.09) 0.07 (0.67) 0.03 (0.87) 0.42 (0.009a) 0.34 (0.18) 0.35 (0.18) 0.28 (0.28) 0.015 (0.95) 0.10 (0.56) 0.005 (0.97) 0.08 (0.63) 0.32 (0.05a) 0.04 (0.82) 0.02 (0.92) 0.09 (0.59) 0.22 (0.19) 0.08 (0.61) 0.24 (0.15)
Statistically significant correlation (p < 0.05) vs. controls (Mann–Whitney test).
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Of the investigated basic laboratory parameters of inflammation, a significant positive correlation between irisin and C-reactive protein (CRP) values (p ¼ 0.009) and sedimentation rate (SR) (p ¼ 0.03) were noticed (Table 2). Evaluating links between irisin levels and other selected proteins, a positive significant correlation with lipocalin-2 (LCN-2) (p ¼ 0.02) was observed (Table 2).
After two weeks of topical treatment with 5% salicylic acid ointment and 0.3% anthralin, the improvement in psoriatic lesions was achieved. The median value of total PASI score after therapy decreased to 8.4 (4.7–12.3) compared with basal PASI 18.8 (10.7–21.8) (Table 1). The median irisin level did not change after therapy (p ¼ 0.79), remaining insignificantly higher than in the controls (p ¼ 0.31) (Table 3, Figure 1). There were no statistically significant differences in the serum irisin levels after treatment among the groups dependent on the severity of psoriasis (Table 5).
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Discussion
Figure 1. Comparison between serum irisin concentrations before and after treatment and control group.
Remarkable difficulty is to take discussion on the results obtained, while to the best of our knowledge in the recent literature not a single study has investigated a potential role of irisin in psoriasis. This study demonstrated that serum irisin levels in patients with psoriasis did not significantly change compared with the healthy controls, however, the value was over 2.5 times higher. Serum irisin levels did not correlate with PASI, also when evaluated according to different psoriasis severity groups. Considering relations between irisin and demographic or clinical data of our study group, we found a significant correlation with age and duration of the disease, meaning the older the patients and the longer the history of his psoriasis, the higher irisin level. Concentration of the investigated adipokine was slightly higher in men than in women but insignificantly. The single data from the literature suggest a
Table 3. The median values and CIs of serum irisin concentrations in psoriatic patients before and after treatment compared with the control group. Statistical analysis using the Mann–Whitney test. Psoriatic patients
Irisin [pg/ml] p (vs. controls)
Controls Median (CI)
Before treatment Median (CI)
After treatment Median (CI)
3.28 (1.18–9.92)
8.32 (0.60–11.01) 0.38
8.19 (1.31–12.00) 0.31
Figure 3. Comparison of irisin levels between groups of patients divided by BMI before treatment.
Table 5. Serum irisin concentrations before treatment in psoriatic patients between three groups ( 20) depending on PASI using the Mann–Whitney test (values “p”). PASI Irisin
20 0.98
Figure 2. Correlation between concentrations of serum irisin and PASI.
Table 4. The median values and CIs of serum irisin concentrations in psoriatic patients before and after treatment depending on PASI score in three groups (20) and depending on the controls. Statistical analysis using the Mann–Whitney test. PASI
Irisin [pg/ml]
before treatment after treatment p (before vs. after treatment)
20 Median (CI)
1.2 (0.3–11.2) 9.5 (0.6–12.3) 0.65
8.8 (0.4–11.9) 8.2 (2.7–13.1) 0.97
7.4 (2.9–11.4) 7.6 (1.9–11.1) 0.85
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JOURNAL OF DERMATOLOGICAL TREATMENT
negative correlation with age and higher irisin level in males than in females but not with psoriasis which is only partially in accordance with our results (6,8). In the absence of data, we can only mention the outcomes from studies in other diseases. Many researchers have reported lower level of irisin level in diabetes and so its association with increased IR and impaired metabolic state (16–19). On the other hand, Choi et al. (17) noted lower irisin level in DM type 2 but elevated in DM type 1. Huh et al. (20) have noted higher levels of irisin in diabetic patients and claimed irisin as an independent predictor of DM. Still the actual physiological role of irisin and even initial findings are being questioned (9,21). This also applies to the role in obesity, diabetes status and MS. Some authors reported a positive correlation with BMI, other no relation or even a negative one (6,22–24). In our study, as for the correlation with metabolic indicators, we found no significance between irisin serum levels and BMI, glucose level and all lipid parameters including LDL-C (low-density lipoprotein cholesterol), HDL-C (high-density lipoprotein cholesterol), TG (triglycerides) and total cholesterol in patients with psoriasis. Several researchers observed positive correlation between irisin and BMI, while a negative relation was reported by Moreno-Navarette et al. (8,24,25). Sanchiz-Gomar et al. (26), similarly to our report, noted that irisin level did not relate to BMI and other biological parameters in obese and diabetic patients. Park et al. (6) and Liu et al. (27) demonstrated a positive correlation between irisin and fasting blood glucose or TG. Park et al. (6) suggested that elevated irisin levels were significantly related to higher risk of MS and it might be an independent predictor of CVD. Other studies reported that irisin was negatively correlated with cholesterol, HDL-C, TG and adiponectin (6,17,22). As mentioned above, the links between adipose tissue or obesity and psoriasis are undeniable. However, even after dividing our patients into groups in terms of different BMI subgroups, we found no significant differences in irisin levels. Taking this into account and also still insignificantly elevated irisin level in our patients we could undermine if irisin is related to metabolic disturbances in psoriasis and we are unable to clarify if it might be an adaptive compensator of any alterations in metabolic homeostasis or promoter of them. On the other hand, our groups of patients divided by BMI were very small, so our outcomes might be unreliable and it needs greater number of subjects in the future investigations. In the present study, in analysis of links with other proteins, irisin level did not correlate with adiponectin, leptin, retinol-binding protein 4 nor fatty-acid proteins, however, we observed a positive statistical relation with lipocalin-2. In our previously published research, we have reported that serum LCN-2 was significantly overexpressed and might be a marker of psoriasis and convey cardiovascular or metabolic risk in psoriatic patients (28). Significance between irisin and LCN-2 is interesting, however, their relations with other parameters are inconsistent, and so it needs further clarification. As for associations with inflammation indicators in our study, irisin level significantly positively correlated with CRP levels and SR in psoriatic patients. This may underlines considering irisin as an acute phase protein and marker of inflammation in psoriasis. However, the lack of similar outcomes enable us the comparison. In our study, after two weeks of topical treatment with keratolytic ointment and anthralin, we found no significant influence on median serum irisin levels in psoriatic patients compared with healthy individuals, despite clinical improvement. However, evaluating dependence on psoriasis activity, irisin level increased insignificantly almost 8 times in group with mild psoriasis. The adipokine is presumably not useful in determining the efficacy of anthralin in psoriatics but has some relevance in mild type of the disease.
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Varying data published provided above could be due to various potential confounders or methodological features. There is still no unanimity on the role of irisin which still seems to be questionable and needs further investigations. The strength of our research is that this is the first study which evaluated irisin in psoriasis and its relations with inflammatory or metabolic parameters. On the other hand, limitations are relatively small population studied and possibly various modified effectors influencing different inflammatory stimuli in psoriasis. Noteworthy would be in the future to examine irisin with larger group of patients with other types of psoriasis, perhaps with subgroup with diabetes or in relation to exercise or diet and explore the influence of various methods of treatment.
Conclusions In conclusion, in this study, serum irisin levels were insignificantly increased in patients with psoriasis reflecting its unclear role in the pathogenesis of this disease. However, we found a positive relation with lipocalin-2 which might be a marker of psoriasis or its comorbidities. No correlations between the myokine and several indicators of metabolic disturbances were observed. Significant positive correlations were noted between irisin and CRP and SR highlighting that the protein could be an indicator of inflammation in psoriasis. Serum irisin level is presumably not useful in evaluating activity of psoriasis and the efficacy of traditional topical treatment. Concluding, data from the literature are sparse or divergent and they refer to diseases other than psoriasis. However, it emphasizes the importance of the present study and the needs to determine an undoubtful role of irisin with respect to obesity-related metabolic disorders in future investigations.
Acknowledgements The authors each state that they have no financial or other relationships that could lead to conflict of interest with the work presented in the submitted paper.
Disclosure statement The authors state that the paper contains original unpublished work and is not being submitted for publication elsewhere at the same time.
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ISSN: 0954-6634 (Print) 1471-1753 (Online) Journal homepage: http://www.tandfonline.com/loi/ijdt20
Serum irisin levels in patients with psoriasis Anna Baran, Hanna Myśliwiec, Paulina Kiluk, Magdalena Świderska & Iwona Flisiak To cite this article: Anna Baran, Hanna Myśliwiec, Paulina Kiluk, Magdalena Świderska & Iwona Flisiak (2017) Serum irisin levels in patients with psoriasis, Journal of Dermatological Treatment, 28:4, 304-308, DOI: 10.1080/09546634.2016.1254327 To link to this article: http://dx.doi.org/10.1080/09546634.2016.1254327
Accepted author version posted online: 27 Oct 2016. Published online: 10 Nov 2016. Submit your article to this journal
Article views: 139
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Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ijdt20 Download by: [Australian Catholic University]
Date: 22 September 2017, At: 08:20
JOURNAL OF DERMATOLOGICAL TREATMENT, 2017 VOL. 28, NO. 4, 304–308 http://dx.doi.org/10.1080/09546634.2016.1254327
ORIGINAL ARTICLE
Serum irisin levels in patients with psoriasis Anna Barana, Hanna Mysliwieca, Paulina Kiluka, Magdalena Swiderskab and Iwona Flisiaka
Downloaded by [Australian Catholic University] at 08:20 22 September 2017
a Department of Dermatology and Venereology, Medical University of Bialystok, Bialystok, Poland; bDepartment of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland
ABSTRACT
ARTICLE HISTORY
Background: Irisin has been proposed to regulate metabolic diseases such as obesity, diabetes or metabolic syndrome which are common comorbidities in psoriasis. Objectives: The aim of this study was to evaluate the serum irisin level in psoriasis and elucidate possible associations with disease activity, inflammatory or metabolic parameters and topical treatment. Methods: Thirty-seven individuals with active plaque-type psoriasis and 15 healthy controls were enrolled. Blood samples were collected before and after two weeks of therapy. Serum irisin concentrations were examined by enzyme-linked immunosorbent assay (ELISA). The results were correlated with psoriasis area and severity index (PASI), body mass index (BMI), inflammatory and biochemical markers, lipid profile and effectiveness of topical treatment. Results: Irisin serum levels were insignificantly increased in psoriatic patients in comparison to the controls (p ¼ 0.38). No significant correlations between investigated adipokine and several indicators of metabolic disorders, nor BMI (p ¼ 0.37) or PASI (p ¼ 0.5) were found. Significant positive correlations with C-reactive protein (CRP) (0.009), lipocalin-2 (p ¼ 0.02), age (p ¼ 0.02) and disease duration (p ¼ 0.008) were noted. After topical treatment, serum irisin level did not significantly change (p ¼ 0.31), despite clinical improvement. Conclusions: Irisin might be a marker of inflammation in psoriatic patients, but may not be a reliable indicator of metabolic conditions, severity of psoriasis nor efficacy of antipsoriatic treatment.
Received 3 August 2016 Accepted 23 October 2016 Published online 11 November 2016
Introduction Psoriasis is a common chronic inflammatory disease, affecting over 2% of the population worldwide. Patients with psoriasis are at higher risk of numerous comorbidities such as obesity, cardiovascular disease (CVD), metabolic syndrome (MS) or insulin resistance (IR) and diabetes mellitus (DM) (1,2). Therefore, currently this dermatosis has been considered as a systemic disorder with impact on psoriatics’ morbidity and mortality. Psoriasis shortens patients’ life by an average of 5–7 years compared with general population due to increased risk of myocardial infarction and thromboembolic events (3). There is a significantly higher prevalence of metabolic syndrome in psoriatic patients ranging from 40% to 65% (4). Interesting, but very complex, is association between psoriasis and obesity, as one of the pivotal components of MS. Adipose tissue is not only an energy reservoir but primarily has metabolic, endocrine and immunomodulatory functions. Psoriatic patients have more than twice higher risk of obesity. On the other hand, obesity often precedes the development of psoriasis and body mass index (BMI) correlates with the risk of this dermatosis. Common genetic background, chronic systemic inflammation and increased synthesis of proinflammatory cytokines or insulin resistance promote endothelial dysfunction and atherosclerosis consequently causing cardiac insufficiency in patients with psoriasis (4,5). Strong relations of psoriasis with numerous metabolic disorders have been leading to investigate potential role of various adipokines or other newer and newer proteins in psoriasis. CONTACT Anna Baran Poland
[email protected]
KEYWORDS
Psoriasis; irisin; myokine; obesity; anthralin
Beside adipose tissue, muscle tissue has been recently identified as an active endocrine organ that also regulates metabolism (6). Irisin, a 12k Da novel myokine comprised of 112 amino acids, €m et al. 2012 (7). was isolated from muscle tissue by Bostro Overexpression of peroxisome proliferator-activated receptor-c coactivator 1a (PGC1a) in skeletal muscle during exercise stimulates cleavage of the membrane protein fibronectin type III domain 5 (FNDC5) which is the precursor of irisin (6,8). This myokine is involved in converting white adipose tissue to brown adipose tissue which increases thermogenesis and may improve systemic metabolism or insulin sensitivity (5,9,10). Irisin is synthesized generally in skeletal muscle, but is also distributed in cardiac muscle, adipose tissue, liver, brain, bones, sebaceous glands, pancreas, kidney and others (4,10). It has been proved that irisin is not only a myokine but adipokine with its auto- and paracrine actions (10,11). It was assumed that irisin could be an indicator of body fat mass as it was elevated in obese subjects in many studies. However, it could be only a compensatory mechanism (10–12). Decreased serum irisin levels were reported to be linked with chronic kidney disease, nonalcoholic fatty liver disease and diabetes (8). Zhang et al. (13) suggested that irisin might be a marker for macrovascular disease in DM. In recent study on mice, the authors have demonstrated a protective effect of treatment with oral irisin on atherosclerosis (14). Irisin seems to be involved in lipid or glucose metabolism and most likely associated with IR, DM, CVD or MS which are common comorbidities in psoriasis (8,10,15). It was also suggested that irisin might play a role in
Department of Dermatology and Venereology, Medical University of Bialystok, 15-540 Bialystok, Zurawia 14 St,
ß 2016 Informa UK Limited, trading as Taylor & Francis Group
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aging process, cognitive capacity or bone metabolism (8,10). Since the discovery of irisin numerous studies have been conducted to assess its role in different diseases. Promising results from other medical fields lead us to explore the novel adipokine in relation to psoriasis, the more there is no data on this topic. The aim of this study was to assess serum irisin levels in patients with plaque-type psoriasis and their relationship with the disease severity, inflammatory or metabolic parameters, other adipokines and topical treatment used.
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Materials and methods The study was conducted on 37 patients (15 females and 22 males) with flare of plaque-type psoriasis, with median age 49 (35–64) years, and 15 sex-, age- and BMI-matched healthy controls. Other types of psoriasis and any other chronic inflammatory or metabolic diseases, which might interfere with the evaluation of psoriasis, were exclusion criteria. None of the participants were under any dietary restriction, systemic nor topical treatment for one month prior to enrollment. BMI was evaluated as weight/ height2 (kg/m2). Psoriasis area and severity index (PASI) was recorded by the same investigator (A.B.) in all patients. The study group was divided depending on the severity – PASI score below 10 defined psoriasis as mild, between 10 and 20 as moderate and above 20 as severe. We divided also our patients into four groups depending on BMI, group 0 related to normal weight (BMI 18.5–24.9) and consisted of 10 persons, 1 – meant overweight (BMI 25–29.9) found in 15 psoriatics, 2 – obesity I grade (BMI 30–34.99) – 8 patients, group 3 – obesity II grade (BMI 35–39.9) included 4 patients. Blood samples were obtained before starting treatment and repeated after two weeks of application of 5% salicylic acid ointment and 0.3% anthralin. All participants gave their signed informed consent before participation and the study was approved by the Bioethical Committee of Medical University of Bialystok. Fasting blood samples were collected from the study and control group using vacutainer tubes and allowed to clot for 30 min before centrifugation for 15 min at 1000 g, then serum was divided for further measurements and stored at 80 C. Irisin serum levels were measured by enzyme-linked immunosorbent assay (ELISA) supplied by BioVendor (catalog no. RAG018R) with detection limit of 1 ng/ml and assay range: 0.001 lg/ml–5 lg/ml. The concentration was determined by interpolation from calibration curves prepared with standard samples provided by the manufacturer. Serum concentrations of other selected adipokines were measured using ELISA supplied by QuantikineV (R&D Systems, Minneapolis, MN) precisely described in our previously published studies. R
Statistical analysis Data analysis are described as mean ± standard deviation (±SD), median value, confidence interval (CI, 25–75% percentile) and percentage when appropriate. The Student’s T-test was used to compare the averages among groups. Correlations were performed using Mann–Whitney U test and the Spearman coefficient correlation for non-normal variables. The Chi-Square test was used for the analysis of qualitative data. Quantitative data divided in categories were ranked using one-way ANOVA Kruskal–Wallis test. Logistic regression was used for multivariate analysis of associations. Values of p < 0.05 were considered statistically significant. Statistical analyzes were conducted using the GraphPad Prism5.0 (La Jolla, CA) and Statistica 12.0 (Statsoft, Tulsa, OK).
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Results The study included 37 patients with active plaque-type psoriasis, 15 women and 22 men with the mean age of 48.6 ± 2.4 (19–84) and 15 age-, sex- and BMI-matched healthy volunteers. The duration of the disease ranged from 1 to 55 years with a mean of 17.4 ± 1.8 and the relapse duration ranged from 0.5 to 2 years with a mean of 4.4. ± 0.9. Median score of BMI was 27 kg/m2 (24–31). Basal PASI score ranged from 5.5 to 32.1 with a median score of 18.8 (10.7–21.8). The demographic, clinical and laboratory data of the study group are summarized in Table 1. Of the 37 patients studied, 7 persons (18.9%) had mild psoriasis (PASI 20). Significant statistical correlations between serum irisin level and age or disease duration were noted (Table 2). The median irisin serum levels in psoriatic patients were 8.23 (0.6–11.01) pg/ml and did not differ significantly (p ¼ 0.38) comparing to the controls, however, it was 2.5 times higher (Figure 1, Table 3). In patients with psoriasis, serum irisin level did not correlate with the PASI score (p ¼ 0.5) nor BMI (p ¼ 0.37) (Figure 2, Tables 2 and 3). Assessing irisin levels depending on the severity of psoriasis in each group of patients, no statistical correlations in comparison to the controls were noted (Table 4). There were no significant relations between the study and control group in terms of liver enzymes activity, glucose nor lipids levels (p > 0.05) (Table 2). There were no significant differences between the groups depending on BMI comparing to the healthy subjects (Figure 3). Table 1. Selected characteristics of the patients. Characteristics SR [mm/h] CRP [mg/l] WBC [103/ml] PLT [103/ml] Glucose level BMI (kg/m2) PASI before treatment PASI after treatment
Median (CI) 16 (7–36) 3.4 (2.1–15.6) 7.3 (6.3–8.7) 203 (164–265) 89 (7–94) 27 (24–31) 18.8 (10.7–21.8) 8.4 (4.7–12.3)
Table 2. Main variables of the study in patients before and after treatment and correlations with serum irisin levels.
Characteristics SR [mm/h] WBC [103/ml] ALT [IU/l] AST [IU/l] PLT [x103/ml] BMI [kg/m2] RBC [x103/ml] Glucose level [mg/dl] CRP [mg/l] Cholesterol [mg/dl] HDL-C [mg/dl] LDL-C [mg/dl] TG [mg/dl] Adiponectin Leptin RBP-4 Lipocalin H-FABP A-FABP YKL-40 Age [years] Relapse duration [months] Disease duration [years] a
Serum irisin before treatment r (p values)
Serum irisin after treatment r (p values)
0.35 (0.03a) 0.05 (0.77) 0.15 (0.38) 0.04 (0.82) 0.05 (0.78) 0.15 (0.37) 0.09 (0.59) 0.18 (0.27) 0.25 (0.13) 0.16 (0.54) 0.06 (0.83) 0.45 (0.07) 0.054 (0.84) 0.04 (0.79) 0.02 (0.91) 0.03 (0.82) 0.37 (0.02a) 0.10 (0.54) 0.23 (0.16) 0.08 (0.63) 0.39 (0.02a) 0.03 (0.83) 0.43 (0.008a)
0.21 (0.21) 0.001 (0.99) 0.0005 (0.99) 0.02 (0.88) 0.001 (0.99) 0.27 (0.09) 0.07 (0.67) 0.03 (0.87) 0.42 (0.009a) 0.34 (0.18) 0.35 (0.18) 0.28 (0.28) 0.015 (0.95) 0.10 (0.56) 0.005 (0.97) 0.08 (0.63) 0.32 (0.05a) 0.04 (0.82) 0.02 (0.92) 0.09 (0.59) 0.22 (0.19) 0.08 (0.61) 0.24 (0.15)
Statistically significant correlation (p < 0.05) vs. controls (Mann–Whitney test).
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Of the investigated basic laboratory parameters of inflammation, a significant positive correlation between irisin and C-reactive protein (CRP) values (p ¼ 0.009) and sedimentation rate (SR) (p ¼ 0.03) were noticed (Table 2). Evaluating links between irisin levels and other selected proteins, a positive significant correlation with lipocalin-2 (LCN-2) (p ¼ 0.02) was observed (Table 2).
After two weeks of topical treatment with 5% salicylic acid ointment and 0.3% anthralin, the improvement in psoriatic lesions was achieved. The median value of total PASI score after therapy decreased to 8.4 (4.7–12.3) compared with basal PASI 18.8 (10.7–21.8) (Table 1). The median irisin level did not change after therapy (p ¼ 0.79), remaining insignificantly higher than in the controls (p ¼ 0.31) (Table 3, Figure 1). There were no statistically significant differences in the serum irisin levels after treatment among the groups dependent on the severity of psoriasis (Table 5).
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Discussion
Figure 1. Comparison between serum irisin concentrations before and after treatment and control group.
Remarkable difficulty is to take discussion on the results obtained, while to the best of our knowledge in the recent literature not a single study has investigated a potential role of irisin in psoriasis. This study demonstrated that serum irisin levels in patients with psoriasis did not significantly change compared with the healthy controls, however, the value was over 2.5 times higher. Serum irisin levels did not correlate with PASI, also when evaluated according to different psoriasis severity groups. Considering relations between irisin and demographic or clinical data of our study group, we found a significant correlation with age and duration of the disease, meaning the older the patients and the longer the history of his psoriasis, the higher irisin level. Concentration of the investigated adipokine was slightly higher in men than in women but insignificantly. The single data from the literature suggest a
Table 3. The median values and CIs of serum irisin concentrations in psoriatic patients before and after treatment compared with the control group. Statistical analysis using the Mann–Whitney test. Psoriatic patients
Irisin [pg/ml] p (vs. controls)
Controls Median (CI)
Before treatment Median (CI)
After treatment Median (CI)
3.28 (1.18–9.92)
8.32 (0.60–11.01) 0.38
8.19 (1.31–12.00) 0.31
Figure 3. Comparison of irisin levels between groups of patients divided by BMI before treatment.
Table 5. Serum irisin concentrations before treatment in psoriatic patients between three groups ( 20) depending on PASI using the Mann–Whitney test (values “p”). PASI Irisin
20 0.98
Figure 2. Correlation between concentrations of serum irisin and PASI.
Table 4. The median values and CIs of serum irisin concentrations in psoriatic patients before and after treatment depending on PASI score in three groups (20) and depending on the controls. Statistical analysis using the Mann–Whitney test. PASI
Irisin [pg/ml]
before treatment after treatment p (before vs. after treatment)
20 Median (CI)
1.2 (0.3–11.2) 9.5 (0.6–12.3) 0.65
8.8 (0.4–11.9) 8.2 (2.7–13.1) 0.97
7.4 (2.9–11.4) 7.6 (1.9–11.1) 0.85
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negative correlation with age and higher irisin level in males than in females but not with psoriasis which is only partially in accordance with our results (6,8). In the absence of data, we can only mention the outcomes from studies in other diseases. Many researchers have reported lower level of irisin level in diabetes and so its association with increased IR and impaired metabolic state (16–19). On the other hand, Choi et al. (17) noted lower irisin level in DM type 2 but elevated in DM type 1. Huh et al. (20) have noted higher levels of irisin in diabetic patients and claimed irisin as an independent predictor of DM. Still the actual physiological role of irisin and even initial findings are being questioned (9,21). This also applies to the role in obesity, diabetes status and MS. Some authors reported a positive correlation with BMI, other no relation or even a negative one (6,22–24). In our study, as for the correlation with metabolic indicators, we found no significance between irisin serum levels and BMI, glucose level and all lipid parameters including LDL-C (low-density lipoprotein cholesterol), HDL-C (high-density lipoprotein cholesterol), TG (triglycerides) and total cholesterol in patients with psoriasis. Several researchers observed positive correlation between irisin and BMI, while a negative relation was reported by Moreno-Navarette et al. (8,24,25). Sanchiz-Gomar et al. (26), similarly to our report, noted that irisin level did not relate to BMI and other biological parameters in obese and diabetic patients. Park et al. (6) and Liu et al. (27) demonstrated a positive correlation between irisin and fasting blood glucose or TG. Park et al. (6) suggested that elevated irisin levels were significantly related to higher risk of MS and it might be an independent predictor of CVD. Other studies reported that irisin was negatively correlated with cholesterol, HDL-C, TG and adiponectin (6,17,22). As mentioned above, the links between adipose tissue or obesity and psoriasis are undeniable. However, even after dividing our patients into groups in terms of different BMI subgroups, we found no significant differences in irisin levels. Taking this into account and also still insignificantly elevated irisin level in our patients we could undermine if irisin is related to metabolic disturbances in psoriasis and we are unable to clarify if it might be an adaptive compensator of any alterations in metabolic homeostasis or promoter of them. On the other hand, our groups of patients divided by BMI were very small, so our outcomes might be unreliable and it needs greater number of subjects in the future investigations. In the present study, in analysis of links with other proteins, irisin level did not correlate with adiponectin, leptin, retinol-binding protein 4 nor fatty-acid proteins, however, we observed a positive statistical relation with lipocalin-2. In our previously published research, we have reported that serum LCN-2 was significantly overexpressed and might be a marker of psoriasis and convey cardiovascular or metabolic risk in psoriatic patients (28). Significance between irisin and LCN-2 is interesting, however, their relations with other parameters are inconsistent, and so it needs further clarification. As for associations with inflammation indicators in our study, irisin level significantly positively correlated with CRP levels and SR in psoriatic patients. This may underlines considering irisin as an acute phase protein and marker of inflammation in psoriasis. However, the lack of similar outcomes enable us the comparison. In our study, after two weeks of topical treatment with keratolytic ointment and anthralin, we found no significant influence on median serum irisin levels in psoriatic patients compared with healthy individuals, despite clinical improvement. However, evaluating dependence on psoriasis activity, irisin level increased insignificantly almost 8 times in group with mild psoriasis. The adipokine is presumably not useful in determining the efficacy of anthralin in psoriatics but has some relevance in mild type of the disease.
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Varying data published provided above could be due to various potential confounders or methodological features. There is still no unanimity on the role of irisin which still seems to be questionable and needs further investigations. The strength of our research is that this is the first study which evaluated irisin in psoriasis and its relations with inflammatory or metabolic parameters. On the other hand, limitations are relatively small population studied and possibly various modified effectors influencing different inflammatory stimuli in psoriasis. Noteworthy would be in the future to examine irisin with larger group of patients with other types of psoriasis, perhaps with subgroup with diabetes or in relation to exercise or diet and explore the influence of various methods of treatment.
Conclusions In conclusion, in this study, serum irisin levels were insignificantly increased in patients with psoriasis reflecting its unclear role in the pathogenesis of this disease. However, we found a positive relation with lipocalin-2 which might be a marker of psoriasis or its comorbidities. No correlations between the myokine and several indicators of metabolic disturbances were observed. Significant positive correlations were noted between irisin and CRP and SR highlighting that the protein could be an indicator of inflammation in psoriasis. Serum irisin level is presumably not useful in evaluating activity of psoriasis and the efficacy of traditional topical treatment. Concluding, data from the literature are sparse or divergent and they refer to diseases other than psoriasis. However, it emphasizes the importance of the present study and the needs to determine an undoubtful role of irisin with respect to obesity-related metabolic disorders in future investigations.
Acknowledgements The authors each state that they have no financial or other relationships that could lead to conflict of interest with the work presented in the submitted paper.
Disclosure statement The authors state that the paper contains original unpublished work and is not being submitted for publication elsewhere at the same time.
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