IL-10 DEFICIT CORRELATES WITH CHRONIC, HYPERSPLENOMEGALY SYNDROME IN MALE CBA J MICE INFECTED WITH SCHISTOSOMA-MANSONI/

Twenty weeks after moderate level infections with Schistosoma mansoni, approximately 20% of male CBA/J mice develop hypersplenomegaly syndro me (HSS) while the rest present with moderate splenomegaly syndrome (M SS). HSS and MSS mice differ pathophysiologically (degree of splenomeg aly, anaemia, ascites, periportal fibrosis, portal hypertension) and i mmunologically with regard to antibodies (idiotypic expression, isotyp e levels) to schistosome soluble egg antigens (SEA), and spleen cell p henotypic profiles. This study compared in vitro proliferative respons es and IL-2, IFN gamma, IL-4, and IL-10 production by spleen cells fro m uninfected mice and mice with acute (8 wk), MSS or HSS schistosomias is mansoni, upon exposure to anti-CD3(epsilon) or SEA. Spleen cells fr om uninfected mice produce IL-2 to anti-CD3(epsilon), but exposure of cells from all three groups of infected mice to anti-CD3(epsilon) or S EA led to only very low levels of supernatant IL-2. Anti-CD3(epsilon)- or SEA-stimulated production of IFN gamma or IL-4, and anti-CD3(epsil on)-stimulated production of IL-10, displayed similar patterns: highes t cytokine production by cells from mice with acute infections and low er levels of production that did not differ between the two chronic gr oups. In contrast, while SEA-stimulated IL-10 production was again hig hest with cells from mice with acute infections, spleen cells from mic e with MSS produced significantly more IL-10 than did those from mice with HSS. This association of low levels of antigen-induced IL-10 with severe pathology is consistent with the theory that IL-10 plays a rol e in the immunoregulation that occurs in chronic schistosomiasis.