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IL-10 regulates liver pathology in acute murine Schistosomiasis mansoni but is not required for immune down-modulation of chronic disease

Item Type:Article
Title:IL-10 regulates liver pathology in acute murine Schistosomiasis mansoni but is not required for immune down-modulation of chronic disease
Creators Name:Wynn, T.A. and Cheever, A.W. and Williams, M.E. and Hieny, S. and Caspar, P. and Kuehn, R. and Mueller, W. and Sher, A.
Abstract:We have used IL-10 gene knockout mice (IL-10T) to examine the role of endogenous IL-10 in the down-modulation of hepatic granuloma formation and lymphocyte responses that occurs in chronic infection with the helminth parasite Schistosoma mansoni. Although IL-10-deficient animals showed 20 to 30% mortality between 8 and 14 wk postinfection, they displayed no alterations in their susceptibility to infection and produced similar numbers of eggs as their wild-type littermates. The IL-10T mice displayed a significant increase in hepatic granuloma size at the acute stage of infection, which was associated with increased IFN-gamma, IL-2, IL-1beta, and TNF-alpha mRNA expression in liver and elevated Th1-type cytokine production by lymphoid cells. Despite developing an enhanced Th1-type cytokine response, the IL-10T mice showed no consistent decrease in their Th2-type cytokine profile. Surprisingly, although granulomatous inflammation was enhanced at the acute stage of infection, the livers of IL-10T mice displayed no significant increase in fibrosis and underwent normal immune down-modulation at the chronic stage of infection. Moreover, the down-modulated state could be induced in IL-10T mice by sensitizing the animals to schistosome eggs before infection, further demonstrating that the major down-regulatory mechanism is not dependent upon IL-10. We conclude that while IL-10 plays an important role in controlling acute granulomatous inflammation, it plays no essential role in the process of immune down-modulation in chronic schistosome infection.
Keywords:Acute Disease, Chronic Disease, Gene Expression Regulation, Granuloma, Inflammation, Interleukin-10, Knockout Mice, Liver, Schistosomiasis mansoni, Animals, Mice
Source:Journal of Immunology
ISSN:0022-1767
Publisher:American Association of Immunologists (U.S.A.)
Volume:160
Number:9
Page Range:4473-4480
Date:1 May 1998
Official Publication:http://www.jimmunol.org/content/160/9/4473
PubMed:View item in PubMed

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