830
Correspondence
100
Chloroquine Inhibits Tumor Necrosis Factor Production by Human Macrophages In Vitro
Reprints or correspondence: Dr. Stephane Picot. Depa rtern ent de Parasitologic Mycologic Medicate et Molecul aire , CNRS URA 1344. Centre Ho spit alier Regional et Univ ersitairc de Grenoble. BP 217. 38043 Grenoble Cedex 9. France. The Journat of Infectious Diseases 1991;164:830 rg 1991 hy The University of Chicago. All rights reserved. 0022-1899/91/6404-0047$01 .00
Infectious Diseases in China Colleagues-In the West, little is known about the spectrum and incidences of infectious diseases that alfect China because little information has been published other than in Chinese journals . As part of a bilateral, academic scholar exchange program between the West Virginia University Health Sciences Center and the Zhejiang Medical University (ZMU) in Hangzhou, PeoReprints or correspondence: D r. R. A. Smego. Jr.. Program in Intern ational Health. Room 2180 HSN . West Virginia University Health Sciences Center. Morgantown. WV 26506. The Journal of Infectious Diseases 1991;164:830-1 © 1991 by The University of Chicago. All rights reserved.
0022-1899/91/6404-0048$01 .00
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Chloroquine (u g/ml) Figure 1. Inhihitory effect of ch loroq uine on tum or necrosi s factor secretion by human macrophages stimulated by 50 ng/ml oflipopolysaccharide. Results of one of five experiments.
ratory . Further prospectives studies on TNF secretion during human malaria should consider the plasma concentration of chloroquine (or its metabolites) as a con founding factor for TNF levels.
Stephane Picot, Francois Peyron, .Iean-Philippe VuiIIez, Benoit Polack, and Pierre Ambroise-Thomas Centre Hosp iialicr Universitaire. Grenoble: Univcrsite Claude Bernard. L ron, France References I. l.erou x-Roel s G . Philippe J , Offner f. Verm eulen A. In-vitro production of cytokines in blood . Lancet 1990:336: 1997. 2. Grau GE . Ta ylor TE. Molyneux ME . e t a l. Tumor necrosis factor an d disease severity in child ren with [alcipanun malaria. N Engl J Med 1989:320: 1586-91 . 3. Picot S. Peyron r , Vuillc z JP , Barhe o . Marsch K. Ambroi se-Th oma s P. Tumor nec rosis facto r production by human mac roph ages stimulated in vitro by Ptasmodiumfalcipannn. Infect Immun 1990:58 :214-6. 4. Kwiatkowski D. Hill A. Sambou I. et al. TNF concen tration in fata l cereb ral. non-fatal cer ebra l. and uncomplicated Plasmodium [alriparulIl malaria. Lancet 1990:336: 1201-4 .
pie's Republic of China, we have been able to share knowledge and statistics on infectious diseases epidemiology in our respective countries. Briefly presented here are infectious disease and related data compiled by the Department oflnfectious Diseases of the First Affiliated Hospital of ZM U (table I). This general medical-surgical hospital, one of four major teaching hospitals of ZMU, has 800 beds and 12 patient care wards. More than 8000 patients are admitted each year, with about 500.000 outpatients seen annually. Hangzhou. located -180 km southwest of Shanghai, is a small city by Chinese standards, with a population of about I million. Zhejiang province (population , 42 million) ranks third among the 30 Chinese provinces in terms of agricultural and industrial productivity. The public health bureau in Zhejiang, as in all other pro vinces, is the governing and controlling body for
Downloaded from http://jid.oxfordjournals.org/ at University of Ulster on July 17, 2015
Colleagues-Much has been published about production oftumor necrosis factor (TNF) by human macrophages. It is thought that blood sampling for TNF mu st be done with great care using a pyrogene-free anticoagulant and blood-collecting system . Then plasma or serum must be rapidl y removed from cells and cooled before assay for TNF [I]. TNF has been implicated in the pathogenesis of several infectiou s and inflammatory processes including cerebral malaria [2]. Because large amounts of chl oroquine circulate in the population living in area s endemic lor malaria and th e fact that this drug easily penetrates macrophages, we inve stigated the influence of chloroquine on TNF production by human macrophages in vitro . Blood was collected from healthy human nonimmune individuals, and monocytes were extracted on a density gradient followed by adherence to plastic dishes, as previously described [3] . Monocytes/macrophages were preincubated lor 2 h with various amounts ofchloroquine (diphosphate salt: Sigma Chemicals , 51. Louis) corresponding to those observed in vivo. Cells were then stimulated with lipopolysaccharide (Escherichia coli 055:B5 : Calbiochern-Behring, La Jolla, CA). After overnight incubation, TNF levels were measured in the supernatant by immunoradiometric assay (IRMA: Medgenix, Fleurus, Belgium). With chloroquine, we observed a dose-dependent significant decrease in TNF production (figure I) . The mechanism remains unknown. This in vitro observation suggests that chloroquine intake may modify TNF levels already measured in vivo during cerebral mal aria [4]. In vivo experiments are in progress in our labo-
JID 1991;164 (October)
Correspondence
100
Chloroquine Inhibits Tumor Necrosis Factor Production by Human Macrophages In Vitro
Reprints or correspondence: Dr. Stephane Picot. Depa rtern ent de Parasitologic Mycologic Medicate et Molecul aire , CNRS URA 1344. Centre Ho spit alier Regional et Univ ersitairc de Grenoble. BP 217. 38043 Grenoble Cedex 9. France. The Journat of Infectious Diseases 1991;164:830 rg 1991 hy The University of Chicago. All rights reserved. 0022-1899/91/6404-0047$01 .00
Infectious Diseases in China Colleagues-In the West, little is known about the spectrum and incidences of infectious diseases that alfect China because little information has been published other than in Chinese journals . As part of a bilateral, academic scholar exchange program between the West Virginia University Health Sciences Center and the Zhejiang Medical University (ZMU) in Hangzhou, PeoReprints or correspondence: D r. R. A. Smego. Jr.. Program in Intern ational Health. Room 2180 HSN . West Virginia University Health Sciences Center. Morgantown. WV 26506. The Journal of Infectious Diseases 1991;164:830-1 © 1991 by The University of Chicago. All rights reserved.
0022-1899/91/6404-0048$01 .00
s..
80
OJ
"0
.s;..,
60
I-
~
Po:
40
.s
20
0 0 0 0
-0
on 0
on
0
0
'"
on
'"
0 0
Chloroquine (u g/ml) Figure 1. Inhihitory effect of ch loroq uine on tum or necrosi s factor secretion by human macrophages stimulated by 50 ng/ml oflipopolysaccharide. Results of one of five experiments.
ratory . Further prospectives studies on TNF secretion during human malaria should consider the plasma concentration of chloroquine (or its metabolites) as a con founding factor for TNF levels.
Stephane Picot, Francois Peyron, .Iean-Philippe VuiIIez, Benoit Polack, and Pierre Ambroise-Thomas Centre Hosp iialicr Universitaire. Grenoble: Univcrsite Claude Bernard. L ron, France References I. l.erou x-Roel s G . Philippe J , Offner f. Verm eulen A. In-vitro production of cytokines in blood . Lancet 1990:336: 1997. 2. Grau GE . Ta ylor TE. Molyneux ME . e t a l. Tumor necrosis factor an d disease severity in child ren with [alcipanun malaria. N Engl J Med 1989:320: 1586-91 . 3. Picot S. Peyron r , Vuillc z JP , Barhe o . Marsch K. Ambroi se-Th oma s P. Tumor nec rosis facto r production by human mac roph ages stimulated in vitro by Ptasmodiumfalcipannn. Infect Immun 1990:58 :214-6. 4. Kwiatkowski D. Hill A. Sambou I. et al. TNF concen tration in fata l cereb ral. non-fatal cer ebra l. and uncomplicated Plasmodium [alriparulIl malaria. Lancet 1990:336: 1201-4 .
pie's Republic of China, we have been able to share knowledge and statistics on infectious diseases epidemiology in our respective countries. Briefly presented here are infectious disease and related data compiled by the Department oflnfectious Diseases of the First Affiliated Hospital of ZM U (table I). This general medical-surgical hospital, one of four major teaching hospitals of ZMU, has 800 beds and 12 patient care wards. More than 8000 patients are admitted each year, with about 500.000 outpatients seen annually. Hangzhou. located -180 km southwest of Shanghai, is a small city by Chinese standards, with a population of about I million. Zhejiang province (population , 42 million) ranks third among the 30 Chinese provinces in terms of agricultural and industrial productivity. The public health bureau in Zhejiang, as in all other pro vinces, is the governing and controlling body for
Downloaded from http://jid.oxfordjournals.org/ at University of Ulster on July 17, 2015
Colleagues-Much has been published about production oftumor necrosis factor (TNF) by human macrophages. It is thought that blood sampling for TNF mu st be done with great care using a pyrogene-free anticoagulant and blood-collecting system . Then plasma or serum must be rapidl y removed from cells and cooled before assay for TNF [I]. TNF has been implicated in the pathogenesis of several infectiou s and inflammatory processes including cerebral malaria [2]. Because large amounts of chl oroquine circulate in the population living in area s endemic lor malaria and th e fact that this drug easily penetrates macrophages, we inve stigated the influence of chloroquine on TNF production by human macrophages in vitro . Blood was collected from healthy human nonimmune individuals, and monocytes were extracted on a density gradient followed by adherence to plastic dishes, as previously described [3] . Monocytes/macrophages were preincubated lor 2 h with various amounts ofchloroquine (diphosphate salt: Sigma Chemicals , 51. Louis) corresponding to those observed in vivo. Cells were then stimulated with lipopolysaccharide (Escherichia coli 055:B5 : Calbiochern-Behring, La Jolla, CA). After overnight incubation, TNF levels were measured in the supernatant by immunoradiometric assay (IRMA: Medgenix, Fleurus, Belgium). With chloroquine, we observed a dose-dependent significant decrease in TNF production (figure I) . The mechanism remains unknown. This in vitro observation suggests that chloroquine intake may modify TNF levels already measured in vivo during cerebral mal aria [4]. In vivo experiments are in progress in our labo-
JID 1991;164 (October)
