Early responses associated with chronic pathology in murine schistosomiasis

Inbred male CBA/J mice infected with Schistosoma mansoni develop either hypersplenomegaly syndrome (HSS) or moderate splenomegaly syndrome (MSS) by 20 weeks of infection. Pathologically and immunologically, MSS and HSS closely parallel the intestinal and hepatosplenic clinical forms of schistosomiasis in humans, respectively. By 6 weeks after infection, mice that eventually will become MSS develop T cell-stimulatory, cross-reactive idiotypes (CRI) while HSS mice never produce CRI. Because presence of CRI is useful to predict degree of chronic pathology, we used this measure to investigate what other early immunological events occurred in animals destined to develop severe morbidity. At 8 weeks of infection, there was a strong inverse correlation between CRI and splenomegaly, egg counts, and liver hydroxyproline. Similarly, phorbol myristate acetate (PMA)- and ionomycin-stimulated intracellular cytokine expression of IL-4, IL-5, and GM-CSF in splenic CD4(+) T cells was inversely correlated with serum CRI and directly correlated with spleen size. In contrast, spleen cell intracellular TNF-alpha and peritoneal cell production of nitric oxide demonstrated positive correlations with CRI and inverse correlations with measures of morbidity. Surprisingly, IL-10 and IFN-gamma were not correlated with CRI levels. These studies link chronic pathology to certain immunological responses during the acute phase of schistosomiasis.