Immunomodulation induced by Ascaris suum extract in mice: effect of anti-interleukin-4 and anti-interleukin-10 antibodies

Scand J Immunol. 1998 Jan;47(1):10-8. doi: 10.1046/j.1365-3083.1998.00251.x.

Abstract

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)-gamma 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-gamma 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • Adjuvants, Immunologic
  • Antibodies, Monoclonal
  • Antigens, Helminth
  • Epitopes
  • Mitogens
  • Interleukin-10
  • Interleukin-4
  • Ovalbumin