Therapeutic effect of interleukin-10 on CCl4-induced hepatic fibrosis in rats.
OBJECTIVE
To study the therapeutic effect of exogenous interleukin-10 on CCl4-induced hepatic fibrosis in rats and its possible mechanisms.


METHODS
Fourty-seven SD rats were randomly divided into control group (group N) and CCl4-induced hepatic fibrosis model group (group C). After CCl4 was given for 9 wk, the model group was divided into three groups. Rats in group M were put to death immediately,rats in group T were treated with IL-10 for another three wk and then put to death, rats in group R recovered after three weeks and were then killed. The degree of hepatic fibrosis was measured by HE staining and histological activity index (HAI). Histological activity index (HAI), change of collagen types I and III were measured by Picrosirius staining. The expression of TNF-alpha, MMP-2 and TIMP-1 in liver tissue was measured by S-P immunohistochemistry.


RESULTS
CCl4- induced experimental rat hepatic fibrosis model was established successfully. The degree of hepatic fibrosis was markedly lower in group T than in groups M and R, and there was no difference between the two groups. The expression of collagen types I and III was significantly suppressed in group T and was slightly suppressed in groups M and R. The positive levels of TNF-alpha, MMP-2 and TIMP-1 in group M increased significantly compared to those in group N (P<0.01). The positive signals decreased significantly in groups T and R (P<0.01),but positive score was significantly lower in group T than in group R (P<0.01).


CONCLUSIONS
Exogenous IL-10 can reverse CCl4-induced hepatic fibrosis in rats. IL-10 may exert its reversible effects on hepatic fibrosis by blocking CCl4-induced inflammation,inhibiting expression of MMP-2 and TIMP-1 and promoting resolution of collagen types I and III.
Huang
Yue-Hong
YH
Department of Gastroenterology, Union Hospital of Fujian Medical University, Fuzhou 350001, Fujian Province, China.
Shi
Mei-Na
MN
Zheng
Wei-Da
WD
Zhang
Li-Juan
LJ
Chen
Zhi-Xin
ZX
Wang
Xiao-Zhong
XZ
D000818:Animals; D002251:Carbon Tetrachloride; D024042:Collagen Type I / Q000032:analysis; D024061:Collagen Type III / Q000032:analysis; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000627:therapeutic use*; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D024042:Collagen Type I; D024061:Collagen Type III; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D002251:Carbon Tetrachloride; D020778:Matrix Metalloproteinase 2