Immune complexes are potent inhibitors of interleukin-12 secretion by human monocytes

Eur J Immunol. 1997 Nov;27(11):2994-3000. doi: 10.1002/eji.1830271136.

Abstract

We have studied the effect of immune complexes (IC) on interleukin (IL)-12 secretion by human monocytes in vitro. Two experimental models of IC were used. IC formed of tetanus toxoid and polyclonal anti-tetanus toxoid antiserum as well as heat-aggregated human serum IgG almost completely inhibited IL-12 (p70 and p40) secretion induced by interferon-gamma and lipopolysaccharide in human blood-derived monocytes. Neutralizing anti-IL-10 antibodies plus indomethacin restored IL-12 secretion in the presence of IC to a high extent, indicating that IL-10 and prostaglandin (PG) partially mediate the IC-induced inhibition of IL-12 secretion. However, neutralization of tumor necrosis factor (TNF)-alpha by specific antibodies also incompletely restored IL-12 secretion. Indeed, monocytes secrete high levels of TNF-alpha upon stimulation by IC. We found that exogenously added TNF-alpha caused a profound inhibition of monocytic IL-12 secretion in the absence of IC, again mediated via the induction of IL-10 and PG. In summary, IC inhibit IL-12 secretion via TNF-alpha-induced IL-10 and PG synthesis. We conclude that IC, typically appearing in the course of chronic inflammatory processes, may influence the balance between Th1 and Th2 responses and may thus contribute to a deprivation of cell-mediated immune responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen-Antibody Complex / physiology*
  • Antigens / pharmacology
  • Cytokines / biosynthesis
  • Cytokines / physiology
  • Hot Temperature
  • Humans
  • Immunoglobulins / metabolism
  • Immunoglobulins / pharmacology
  • Immunosuppressive Agents / pharmacology*
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / physiology
  • Interleukin-12 / antagonists & inhibitors*
  • Interleukin-12 / immunology
  • Interleukin-12 / metabolism*
  • Monocytes / immunology
  • Monocytes / metabolism*
  • Prostaglandins / biosynthesis
  • Prostaglandins / physiology
  • Tetanus Antitoxin / pharmacology
  • Tetanus Toxoid / immunology
  • Tetanus Toxoid / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Antigen-Antibody Complex
  • Antigens
  • Cytokines
  • Immunoglobulins
  • Immunosuppressive Agents
  • Prostaglandins
  • Tetanus Antitoxin
  • Tetanus Toxoid
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-12