Regulatory role of interleukin-10 and interferon-gamma in severe hepatic central and peripheral fibrosis in humans infected with Schistosoma japonicum.
BACKGROUND
Schistosoma japonicum is the most pathogenic agent of hepatosplenic schistosomiasis. It causes fibrosis of the central (CentF) and peripheral (PerF) portal areas. We investigated whether CentF and PerF in Chinese fishermen infected with S. japonicum were associated with an abnormal production of cytokines and chemokines that, in experimental models, have been implicated in the regulation of fibrosis.


METHODS
Cytokines were measured by enzyme-linked immunosorbent assay in cultures of peripheral blood mononuclear cells from 127 patients, after stimulation with S. japonicum egg antigens. Data were analyzed by logistic regression that included age, sex, number of treatment episodes, alcohol use, and exposure as covariates.


RESULTS
CentF was associated with low levels of interleukin (IL)-10 (P= .0004), regulated on activation normally T cell expressed and secreted (P= .0004), and macrophage inflammatory protein-1alpha (P= .007). In a multivariate analysis, only IL-10 was associated with CentF (odds ratio [OR], 10.8; 95% confidence interval [CI], 3.2-38; P= .0004). Splenomegaly was also associated with low IL-10 production and, independently, with CentF. In multivariate analysis, PerF was associated with low production of interferon (IFN)-gamma (OR, 8.2; 95% CI, 2-33; P= .0035) but not with production of IL-10.


CONCLUSIONS
IL-10 is associated with protection against central fibrosis, because of its anti-inflammatory and antifibrosis effects. IFN-gamma is associated with protection against PerF, which depends more on egg load and egg-associated toxicity.
Arnaud
Violaine
V
INSERM, Unité 399, and 2Aix Marseille Université, Faculté de Médecine, Marseille, France. v.arnaud@netcourrier.com
Li
Jun
J
Wang
Yuanyuan
Y
Fu
Xiao
X
Mengzhi
Shi
S
Luo
Xinsong
X
Hou
Xunya
X
Dessein
Helia
H
Jie
Zhou
Z
Xin-Ling
Yu
Y
He
Hongbin
H
McManus
Donald P
DP
Li
Yuesheng
Y
Dessein
Alain
A
D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008103:Liver Cirrhosis / Q000276:immunology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012549:Schistosoma japonicum / Q000276:immunology*; D012554:Schistosomiasis japonica / Q000276:immunology*; D013163:Splenomegaly / Q000276:immunology
D016753:Interleukin-10; D007371:Interferon-gamma