Pharmacology and therapeutics
Serum levels of adipocytokines in psoriasis patients receiving tumor necrosis factor-a inhibitors: results of a retrospective analysis Anna Campanati1,*, MD, Giulia Ganzetti1,*, MD, Katia Giuliodori1, MD, Maurizio Marra2, PHD, Annarita Bonfigli2, PHD, Roberto Testa3, MD, and Annamaria Offidani1, MD
1 Dermatology Unit, Department of Clinical and Molecular Sciences, Polytechnic Marche University, Ancona, Italy, 2 Metabolic Diseases and Diabetology Unit, Italian National Research Center on Aging (INRCA), Ancona, Italy, and 3Experimental Models in Clinical Pathology, INRCA, Ancona, Italy
Correspondence Anna Campanati, MD Dermatology Unit Department of Clinical and Molecular Sciences Marche Polytechnic University Ancona 60020 Italy E-mail: [email protected] *These authors contributed equally to this work. Conflicts of interest: None.
Abstract Background Adipocytokines are bioactive molecules that are deeply involved in the occurrence of atherosclerosis, obesity, and autoimmune inflammatory diseases. Objectives This study was conducted to evaluate the effects of tumor necrosis factor-a (TNF-a) inhibitors on serum levels of adipocytokines in patients with chronic plaque psoriasis. Methods Serum levels of adiponectin, resistin, visfatin, leptin, TNF-a, and interleukin-6 (IL-6) were evaluated in sera obtained from 47 patients with psoriasis, both at baseline and after they had received TNF-a inhibitors for 24 weeks. Equivalent data were obtained for 39 control subjects matched by age, sex, body mass index, waist : hip ratio, geographical origin, Mediterranean dietary habits, and smoking habits. Results At baseline, mean serum levels of TNF-a, IL-6, leptin, resistin, and visfatin were higher in the psoriasis group than in healthy controls; these differences were statistically significant (P < 0.05). Conversely, mean serum levels of adiponectin were significantly lower in patients with psoriasis than in controls (P < 0.0001). Serum levels of adipocytokines did not linearly correlate with anthropometric indices in psoriasis patients (P > 0.05), except in the case of leptin, for which serum levels were related to waist : hip ratio in both men and women (P < 0.05). After 24 weeks of treatment, although serum levels of proinflammatory adipocytokines were decreased, only that of leptin showed a statistically significant reduction (P = 0.0003). Serum levels of adiponectin, an antiinflammatory adipocytokine, were only mildly increased and persisted at a significantly
doi: 10.1111/ijd.12706
lower level than in healthy controls (P > 0.005). Conclusions Patients with psoriasis show an imbalance between pro- and anti-inflammatory adipocytokines, which is reduced but not normalized after administration of TNF-a inhibitors for 24 weeks. This partial rebalancing seems to be mainly related to a reduction in proinflammatory adipocytokines, rather than an increase in anti-inflammatory adipocytokines.
Introduction Psoriasis is a chronic, relapsing, inflammatory, immune mediated disease that affects approximately 3% of the White population.1,2 Like other cutaneous disorders,3,4 psoriasis is associated with more than just skin disease: recent studies have focused on the association between psoriasis and metabolic syndrome and have suggested that psoriasis may be considered as an independent risk factor for cardiovascular disease, particularly in young adults.5–10 Obesity is a chronic disease that leads to increased morbidity and mortality; its prevalence is increased in psoriasis patients.7 ª 2015 The International Society of Dermatology
According to the most recent scientific evidence, the visceral adipose tissue not only serves to store energy but is also an important player in the immune system and represents an active endocrine organ producing proinflammatory cytokines (tumor necrosis factor-a [TNF-a], interleukin-6 [IL-6]), free fatty acids, procoagulant factors, and bioactive molecules called adipocytokines.11,12 Adipocytokines modulate the appetite–energy balance, immunity, insulin sensitivity, angiogenesis, blood pressure, and lipid metabolism through autocrine, paracrine, and endocrine avenues: TNF-a, IL-6, leptin, visfatin, and resistin appear to exert proinflammatory effects, whereas adiponectin has anti-inflammatory properties.12–14 International Journal of Dermatology 2015
1
2
Pharmacology and therapeutics
Adipocytokine serum levels in psoriasis
Psoriasis and obesity share the same imbalance between pro- and anti-inflammatory adipocytokines, which leads to a low and persistent inflammatory status.14,15 Although it is well known that TNF-a inhibitors are able to improve psoriasis,16–19 few data have been reported on their effects on serum levels of adipocytokines, and none have focused specifically on psoriasis.20,21 Thus, the aim of this study was to investigate the effects of 24 weeks of anti-TNF-a treatment on serum levels of adipocytokines in psoriasis patients. Materials and methods Design of the study This study was designed as a retrospective case–control analysis and was approved by the Marche Polytechnic University Ethical Committee. It was conducted in accordance with the Declaration of Helsinki. Study population We selected 47 serum samples (previously stored at 80 °C) obtained from patients with stable, moderate to severe plaque psoriasis, who had received anti-TNF-a treatment for 24 weeks between January and December 2011. Frozen blood samples obtained from 39 healthy subjects were used as control material. Subjects were excluded from the study if they had diabetes, were overweight, or had a previous diagnosis of metabolic syndrome. Patients with erythrodermic pustular psoriasis and psoriatic arthritis were also excluded. All included subjects had been free from any therapy that might interfere with lipid and glucose metabolism; moreover, psoriasis patients were required not to have received systemic conventional treatments (psoralen with ultraviolet A [PUVA] therapy, acitretin, methotrexate, cyclosporine) for at least four weeks prior to the study and to be na€ıve to biological treatments. Both study and control groups were matched for age (range: 18–65 years), sex, body mass index (BMI) (
Serum levels of adipocytokines in psoriasis patients receiving tumor necrosis factor-a inhibitors: results of a retrospective analysis Anna Campanati1,*, MD, Giulia Ganzetti1,*, MD, Katia Giuliodori1, MD, Maurizio Marra2, PHD, Annarita Bonfigli2, PHD, Roberto Testa3, MD, and Annamaria Offidani1, MD
1 Dermatology Unit, Department of Clinical and Molecular Sciences, Polytechnic Marche University, Ancona, Italy, 2 Metabolic Diseases and Diabetology Unit, Italian National Research Center on Aging (INRCA), Ancona, Italy, and 3Experimental Models in Clinical Pathology, INRCA, Ancona, Italy
Correspondence Anna Campanati, MD Dermatology Unit Department of Clinical and Molecular Sciences Marche Polytechnic University Ancona 60020 Italy E-mail: [email protected] *These authors contributed equally to this work. Conflicts of interest: None.
Abstract Background Adipocytokines are bioactive molecules that are deeply involved in the occurrence of atherosclerosis, obesity, and autoimmune inflammatory diseases. Objectives This study was conducted to evaluate the effects of tumor necrosis factor-a (TNF-a) inhibitors on serum levels of adipocytokines in patients with chronic plaque psoriasis. Methods Serum levels of adiponectin, resistin, visfatin, leptin, TNF-a, and interleukin-6 (IL-6) were evaluated in sera obtained from 47 patients with psoriasis, both at baseline and after they had received TNF-a inhibitors for 24 weeks. Equivalent data were obtained for 39 control subjects matched by age, sex, body mass index, waist : hip ratio, geographical origin, Mediterranean dietary habits, and smoking habits. Results At baseline, mean serum levels of TNF-a, IL-6, leptin, resistin, and visfatin were higher in the psoriasis group than in healthy controls; these differences were statistically significant (P < 0.05). Conversely, mean serum levels of adiponectin were significantly lower in patients with psoriasis than in controls (P < 0.0001). Serum levels of adipocytokines did not linearly correlate with anthropometric indices in psoriasis patients (P > 0.05), except in the case of leptin, for which serum levels were related to waist : hip ratio in both men and women (P < 0.05). After 24 weeks of treatment, although serum levels of proinflammatory adipocytokines were decreased, only that of leptin showed a statistically significant reduction (P = 0.0003). Serum levels of adiponectin, an antiinflammatory adipocytokine, were only mildly increased and persisted at a significantly
doi: 10.1111/ijd.12706
lower level than in healthy controls (P > 0.005). Conclusions Patients with psoriasis show an imbalance between pro- and anti-inflammatory adipocytokines, which is reduced but not normalized after administration of TNF-a inhibitors for 24 weeks. This partial rebalancing seems to be mainly related to a reduction in proinflammatory adipocytokines, rather than an increase in anti-inflammatory adipocytokines.
Introduction Psoriasis is a chronic, relapsing, inflammatory, immune mediated disease that affects approximately 3% of the White population.1,2 Like other cutaneous disorders,3,4 psoriasis is associated with more than just skin disease: recent studies have focused on the association between psoriasis and metabolic syndrome and have suggested that psoriasis may be considered as an independent risk factor for cardiovascular disease, particularly in young adults.5–10 Obesity is a chronic disease that leads to increased morbidity and mortality; its prevalence is increased in psoriasis patients.7 ª 2015 The International Society of Dermatology
According to the most recent scientific evidence, the visceral adipose tissue not only serves to store energy but is also an important player in the immune system and represents an active endocrine organ producing proinflammatory cytokines (tumor necrosis factor-a [TNF-a], interleukin-6 [IL-6]), free fatty acids, procoagulant factors, and bioactive molecules called adipocytokines.11,12 Adipocytokines modulate the appetite–energy balance, immunity, insulin sensitivity, angiogenesis, blood pressure, and lipid metabolism through autocrine, paracrine, and endocrine avenues: TNF-a, IL-6, leptin, visfatin, and resistin appear to exert proinflammatory effects, whereas adiponectin has anti-inflammatory properties.12–14 International Journal of Dermatology 2015
1
2
Pharmacology and therapeutics
Adipocytokine serum levels in psoriasis
Psoriasis and obesity share the same imbalance between pro- and anti-inflammatory adipocytokines, which leads to a low and persistent inflammatory status.14,15 Although it is well known that TNF-a inhibitors are able to improve psoriasis,16–19 few data have been reported on their effects on serum levels of adipocytokines, and none have focused specifically on psoriasis.20,21 Thus, the aim of this study was to investigate the effects of 24 weeks of anti-TNF-a treatment on serum levels of adipocytokines in psoriasis patients. Materials and methods Design of the study This study was designed as a retrospective case–control analysis and was approved by the Marche Polytechnic University Ethical Committee. It was conducted in accordance with the Declaration of Helsinki. Study population We selected 47 serum samples (previously stored at 80 °C) obtained from patients with stable, moderate to severe plaque psoriasis, who had received anti-TNF-a treatment for 24 weeks between January and December 2011. Frozen blood samples obtained from 39 healthy subjects were used as control material. Subjects were excluded from the study if they had diabetes, were overweight, or had a previous diagnosis of metabolic syndrome. Patients with erythrodermic pustular psoriasis and psoriatic arthritis were also excluded. All included subjects had been free from any therapy that might interfere with lipid and glucose metabolism; moreover, psoriasis patients were required not to have received systemic conventional treatments (psoralen with ultraviolet A [PUVA] therapy, acitretin, methotrexate, cyclosporine) for at least four weeks prior to the study and to be na€ıve to biological treatments. Both study and control groups were matched for age (range: 18–65 years), sex, body mass index (BMI) (
