The role of cytokines in the pathogenesis of hepatic granulomatous disease in Schistosoma mansoni infected mice.
Cytokines are important in the cell-mediated response to Schistosoma mansoni eggs. We have found that Th2 cytokine responses (e.g. IL-4 and IL-5) are augmented after egg laying begins while Th1 responses (IL-2 and IFN-gamma) are down regulated in S. mansoni infected mice. Treatment of mice with anti-IL-5 monoclonal antibodies (Mab) suppressed the eosinophil response almost completely but did not affect granuloma size and slightly increased hepatic fibrosis. Anti-IL-4 treatment abolished IgE responses in infected mice and decreased hepatic fibrosis slightly. Anti-IFN-gamma treatment had no effect on hepatic pathology. Anti-IL-2 treatment decreased granuloma size significantly and decreased hepatic fibrosis markedly. Anti-IL-2 treatment dramatically decreased IL-5 secretion by splenic cells in vitro and decreased peripheral blood and tissue eosinophilia. In contrast IL-4 secretion was unaffected and serum IgE was normal or increased. IL-2 and IFN-gamma secretion by splenic cells of treated mice were slightly but not significantly increased suggesting that anti-IL-2 treatment is affecting Th2 rather than Th1 responses.
Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, MD 20892.
A W
AW
Cheever
Y
Y
Xu
J G
JG
Macedonia
T
T
Cox
S
S
Hieny
A
A
Sher
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000502:physiology*; D005260:Female; D005355:Fibrosis; D006099:Granuloma / Q000469:parasitology* / Q000503:physiopathology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008109:Liver Diseases, Parasitic / Q000469:parasitology* / Q000473:pathology; D051379:Mice; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors; D012555:Schistosomiasis mansoni / Q000503:physiopathology*; D013154:Spleen / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D016207:Cytokines; D007378:Interleukins; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma