Immunomodulation Induced by Ascaris suum Extract in Mice: Effect of Anti‐Interleukin‐4 and Anti‐Interleukin‐10 Antibodies

• Published in: Scandinavian journal of immunology 1998-01, Vol.47 (1), p.10-18
• Main Authors: Macedo, M S, Faquim-Mauro, E, Ferreira, A P, Abrahamsohn, I A
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - pharmacology; Animals; Antibodies, Monoclonal - pharmacology; Antigens, Helminth - immunology; Ascaris suum - immunology; Drug Synergism; Epitopes - immunology; Interleukin-10 - immunology; Interleukin-10 - metabolism; Interleukin-4 - immunology; Interleukin-4 - metabolism; Male; Mice; Mice, Inbred DBA; Mitogens - pharmacology; Neutralization Tests; Ovalbumin - immunology; Ovalbumin - pharmacology
• ISSN: 0300-9475; 1365-3083
• DOI: 10.1046/j.1365-3083.1998.00251.x

Simultaneous immunization of mice with an Ascaris suum extract (Asc) and ovalbumin (OA) markedly affects the immune response to OA. The role of interleukin (IL)‐4 and IL‐10 induced by Asc immunization on the modulation of antigen‐specific and mitogen‐induced responses was investigated following single or combined cytokine‐specific monoclonal antibody (MoAb) treatment of mice before immunization with OA + Asc. Immediate hypersensitivity reactions to aggregated OA and OA‐specific immunoglobulin (Ig)G2a antibody production were completely restored only when both IL‐4 and IL‐10 were neutralized. These findings were associated with enhanced interferon (IFN)‐γ secretion by OA‐stimulated lymph node (LN) cells. In addition, the Asc‐specific cytokine response in anti‐IL‐4 plus anti‐IL‐10 MoAb treated mice was shifted towards a Th1 phenotype, with an increase in IFN‐γ and IL‐2 levels and a decrease in IL‐4, but not in IL‐10, levels. Consequently, Asc‐specific IgG2a antibody production increased, whereas IgE titres diminished in these animals. 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 Asc‐immunized mice appears to be essentially mediated by an IL‐4‐dependent 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 not 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 Asc components concomitant to OA immunization has a strong suppressive effect on the priming stage of OA‐specific Th1 type response.