IMMUNOMODULATION INDUCED BY ASCARIS-SUUM EXTRACT IN MICE - EFFECT OF ANTI-INTERLEUKIN-4 AND ANTI-INTERLEUKIN-10 ANTIBODIES

Simultaneous immunization of mice with an Ascaris suum extract (Asc) a nd ovalbumin (OA) markedly affects the immune response to OA. The role of interleukin (IL)-4 and IL-10 induced by Asc immunization on the mo dulation of antigen-specific and mitogen-induced responses was investi gated following single or combined cytokine-specific monoclonal antibo dy (MoAb) treatment of mice before immunization with OA + Asc. Immedia te hypersensitivity reactions to aggregated OA and OA-specific immunog lobulin (Ig)G2a antibody production were completely restored only when both IL-4 and IL-10 were neutralized, These findings were associated with enhanced interferon (TFN)-gamma secretion by OA-stimulated lymph node (LN) cells. In addition, the Asc-specific cytokine response in an ti-IL-4 plus anti-IL-10 MoAb treated mice was shifted towards a Th1 ph enotype, with an increase in IFN-gamma and IL-2 levels and a decrease in IL-4, but not in IL-10, levels. Consequently, Asc-specific IgG2a an tibody production increased, whereas IgE titres diminished in these an imals. These results indicate that IL-4 and IL-10 act together in the Asc-induced mechanism of antigen-specific pansuppression. In contrast, modulation of Concanavalin A (Con A)-induced cytokine responses in As c-immunized mice appears to be essentially mediated by an IL-4-depende nt mechanism, since the neutralization of just IL-4 (and not of IL-10) , either in vivo or in vitro, changed the cytokine profile from a Th2 towards a Th1 type. However, OA and Asc-specific cell responses were n ot modified by either anti-IL-4 or by anti-IL-4 + anti-IL-10 MoAbs in vitro treatments, suggesting that the induction of a Th2 response to A sc components concomitant to OA immunization has a strong suppressive effect on the priming stage of OA-specific Th1 type response.