SCHISTOSOMA-MANSONI-INFECTED MICE SHOW AUGMENTED HEPATIC-FIBROSIS ANDSELECTIVE-INHIBITION OF LIVER CYTOKINE PRODUCTION AFTER TREATMENT WITH ANTI-NK1.1 ANTIBODIES

Gamma interferon (IFN-gamma) plays an immunoregulatory role at differe nt stages of the experimental Schistosoma mansoni-driven processes in mice through its ability to induce cell cytotoxicity against the paras ite larvae and to reduce established hepatic fibrosis. The role of Nat ural Killer (NK) cells, as a possible major source of IFN-gamma, has n ever been studied during the entire course of murine schistosomiasis. In this paper, we investigated the consequences of in vivo NK cell dep letion, maintained during 17 weeks of infection, on both hepatic granu loma development and immunological parameters. We found that NK cell d epletion following anti-NK1.1 monoclonal antibody (mAb) injections led to an increase of hepatic collagen content in the late stages of gran uloma formation and to the diminution of interleukin 12 (IL-12) p40 an d IL-7 mRNA expression in the livers. The hepatic mRNA expression of o ther cytokines (IFN-gamma, tumor necrosis factor alpha [TNF-alpha] and IL-4), as well as humoral and cytokine responses in sera, were not si gnificantly different between control monoclonal antibody (CmAb) and a nti-NK1.1-treated mice. Thus, we demonstrate that the anti-NK1.1 treat ment might induce alterations of regulatory mechanisms, detectable at a late stage of a chronic process in immunocompetent mice. Copyright ( C) 1996 Elsevier Science B.V.