Anti-inflammatory properties of human serum IgA: induction of IL-1 receptor antagonist and Fc alpha R (CD89)-mediated down-regulation of tumour necrosis factor-alpha (TNF-alpha) and IL-6 in human monocytes

Clin Exp Immunol. 1996 Sep;105(3):537-43. doi: 10.1046/j.1365-2249.1996.d01-793.x.


A deregulated expression and/or release of large amounts of inflammatory cytokines such as IL-1 and TNF-alpha accounts for most pathophysiological events in a variety of systemic inflammatory diseases, the effect being mediated by the interaction of these cytokines with their respective receptors. IL-1 receptor antagonist (IL-1Ra), mainly produced by monocytes/macrophages, is an inhibitor of IL-1 activity. The present study shows that human serum IgA induces significant IL-1Ra release in human peripheral blood mononuclear cells and adherent monocytes. IgA induced higher levels of IL-1Ra than Haemophilus influenzae type b (Hib) expressing lipopolysaccharide (LPS), purified LPS or phorbol myristate acetate (PMA), without induction of IL-1 beta release, and even inhibited LPS-induced IL-1 beta release. Induction of IL-1Ra by IgA could be detected both at the mRNA and protein levels in resting and activated monocytes. Ligation of Fc alpha R with MoAb My-43 or treatment with human serum IgA induced protein tyrosine phosphorylation in human monocytes, and herbimycin A, a specific inhibitor of protein tyrosine kinase activity, inhibited IgA-induced IL-1Ra production, suggesting that Fc alpha R-mediated induction of tyrosine phosphorylation is required for the IgA-induced stimulation of IL-1Ra release. In addition, triggering of Fc alpha R with MoAb specifically down-regulated TNF-alpha and IL-6 release in human monocytes activated with Hib. By the induction of IL-1Ra and down-regulation of the release of inflammatory cytokines such as IL-1 beta, TNF-alpha and IL-6, interaction of IgA with human monocytes may actively contribute to the regulation of the inflammatory response.

MeSH terms

  • Adult
  • Antigens, CD / drug effects*
  • Antigens, CD / physiology*
  • Down-Regulation / immunology*
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin A / pharmacology*
  • Inflammation Mediators / blood
  • Inflammation Mediators / pharmacology*
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / biosynthesis
  • Interleukin-6 / biosynthesis*
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism
  • Receptors, Fc / drug effects*
  • Receptors, Fc / physiology*
  • Receptors, Interleukin-1 / antagonists & inhibitors*
  • Sialoglycoproteins / biosynthesis*
  • Tumor Necrosis Factor-alpha / biosynthesis*


  • Antigens, CD
  • Fc(alpha) receptor
  • IL1RN protein, human
  • Immunoglobulin A
  • Inflammation Mediators
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Interleukin-6
  • Receptors, Fc
  • Receptors, Interleukin-1
  • Sialoglycoproteins
  • Tumor Necrosis Factor-alpha
  • Protein-Tyrosine Kinases