IL-12 down-regulates autoantibody production in mercury-induced autoimmunity

J Immunol. 1998 Feb 15;160(4):1612-7.

Abstract

In genetically susceptible H-2s mice, subtoxic doses of mercuric chloride (HgCl2) induce a complex autoimmune syndrome characterized by the production of anti-nucleolar IgG Abs, lymphoproliferation, increased serum levels of IgG1 and IgE Abs, and renal Ig deposits. Mercury-induced autoimmunity in H-2s mice provides a useful model for chemically related autoimmunity in humans. The increase in serum IgG1 and IgE, which are under IL-4 control, suggests a role for the Th2 subset in this syndrome. The IL-12 cytokine induces T cell proliferation and IFN-gamma production and is necessary for differentiation of naive T cells into the Th1 subset. To gain an understanding of T cell control in this syndrome and, in particular, Th1/Th2 regulation, we assessed the effect of IL-12 administration in mercury-induced autoimmunity. Groups of A.SW mice (H-2s) received HgCl2 plus IL-12, HgCl2 alone, or IL-12 alone. IL-12 treatment resulted in a dramatic reduction of the anti-nucleolar Ab titers. IL-12 also inhibited the HgCl2-induced serum IgG1 increase, but, in contrast, did not significantly affect IgE induction in this model. This observation may be related to our unexpected finding that IL-12 further potentiated the HgCl2-triggered IL-4 induction in this model. The levels of renal Ig deposits were similar in mice receiving HgCl2 alone or HgCl2 plus IL-12. Our results indicate that IL-12 can down-regulate the autoimmune component of this experimental syndrome and that the various manifestations of mercury-induced autoimmunity are independently regulated.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Antibodies, Antinuclear / biosynthesis*
  • Antibodies, Antinuclear / drug effects
  • Autoimmune Diseases / chemically induced*
  • Autoimmune Diseases / immunology
  • B-Lymphocytes / drug effects
  • Cell Nucleolus / immunology
  • Down-Regulation / immunology*
  • Female
  • Immunoglobulin E / blood
  • Immunoglobulin E / drug effects
  • Immunoglobulin G / blood
  • Immunoglobulin G / classification
  • Immunoglobulin G / metabolism
  • Immunosuppressive Agents / pharmacology
  • Injections, Subcutaneous
  • Interleukin-12 / administration & dosage
  • Interleukin-12 / pharmacology*
  • Interleukin-4 / biosynthesis
  • Kidney / immunology
  • Kidney / metabolism
  • Lymphocyte Count / drug effects
  • Mercuric Chloride / toxicity*
  • Mice
  • Mice, Inbred A
  • Spleen / cytology

Substances

  • Adjuvants, Immunologic
  • Antibodies, Antinuclear
  • Immunoglobulin G
  • Immunosuppressive Agents
  • Interleukin-12
  • Interleukin-4
  • Immunoglobulin E
  • Mercuric Chloride