IL-10 REGULATES LIVER PATHOLOGY IN ACUTE MURINE SCHISTOSOMIASIS-MANSONI BUT IS NOT REQUIRED FOR IMMUNE DOWN-MODULATION OF CHRONIC DISEASE

We have used IL-10 gene knockout mice (IL-10T) to examine the role of endogenous DL-IO in the down-modulation of hepatic granuloma formation and lymphocyte responses that occurs in chronic infection with the he lminth parasite Schistosoma mansoni, Although IL-10-deficient animals showed 20 to 30% mortality between 8 and 14 wk postinfection, they dis played no alterations in their susceptibility to infection and produce d similar numbers of eggs as their wild-type littermates. The IL-10T m ice displayed a significant increase in hepatic granuloma size at the acute stage of infection, which was associated with increased IFN-gamm a, IL-2, IL-1 beta, and TNF-alpha mRNA expression in liver and elevate d Th1-type cytokine production by lymphoid cells, Despite developing a n enhanced Th1-type cytokine response, the IL-10T mice showed no consi stent decrease in their Th2-type cytokine profile, Surprisingly, altho ugh granulomatous inflammation was enhanced at the acute stage of infe ction, the livers of IL-10T mice displayed no significant increase in fibrosis and underwent normal immune down-modulation at the chronic st age of infection, Moreover, the down-modulated state could be induced in IL-10T mice by sensitizing the animals to schistosome eggs before i nfection, further demonstrating that the major down-regulatory mechani sm is not dependent upon IL-10. We conclude that while IL-10 plays an important role in controlling acute granulomatous inflammation, it pla ys no essential role in the process of immune down-modulation in chron ic schistosome infection.