RESUMO
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.
Assuntos
Citocinas/fisiologia , Granuloma/parasitologia , Hepatopatias Parasitárias/parasitologia , Esquistossomose mansoni/fisiopatologia , Animais , Células Cultivadas , Citocinas/antagonistas & inibidores , Feminino , Fibrose , Granuloma/fisiopatologia , Interferon gama/antagonistas & inibidores , Interferon gama/biossíntese , Interleucinas/antagonistas & inibidores , Interleucinas/biossíntese , Hepatopatias Parasitárias/patologia , Camundongos , Receptores de Interleucina-2/antagonistas & inibidores , Baço/patologia , Linfócitos T Auxiliares-Indutores/imunologiaRESUMO
The in vitro lymphocyte blastogenesis capabilities of patients with schistosomiasis mansoni were tested against phytohemagglutinin (PHA), Candida albicans extract,and soluble preparations of schistosome eggs (SEA), adult worms (SWAP), or cercariae (CAP). When patients lymphocytes were cultured un medium which contained 5 percent human (homologous) normal (uninfected) serum, they responded well to PHA and Candida extract. The responses induced by SEA were maximal in patients with early Schistosma mansoni infections, while reactivity against SWAP and CAP increased during chronic infection. These responses, induced by the Schistosome-derived antigenic preparations,were suppressed if the homologous normal serum supplement of the culture medium was replaced with either the patient's own (autologous) serum, or that of another S. mansoni patient. All sera were heat-inactivated (56 degree C/ 30 min) prior to use. In contrast, responses against the non-specific mitogen (PHA) and the unrelated antigen (Candida extract), were not altered by these changes of the serum supplementation of the media. The degree of suppression by patient serum was not changedby increasing the serum percentage in the medium from 5 percent to 25 percent. The suppressive effects of patient sera on responses induced by SEA and SWAP were increased in relationship to the duration of the serum donor's S. mansoni infection. Preincubation of lymphocytes in suppressive patient sera for 30 min at 37 degree C did not reduce the expected level of responsiveness if the cells were subsequently cultured in homologous-normal serum supplemented medium. The data indicate that during S. mansoni infection patients develop serum component(s) which specifically interfere with the responsiveness of their lymphocytes in regard to certain schistosome-derived antigenic preparations. The immunoregulatory events described could participate in the modulation of immunopathology, the maintenance of chronic worm survival and the prevention of full expression of protective immune responses. (AU)