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Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1996 Sep;105(3):537–543. doi: 10.1046/j.1365-2249.1996.d01-793.x

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

H M WOLF *, I HAUBER *, H GULLE *, A SAMSTAG *, M B FISCHER *, R U AHMAD *, M M EIBL *
PMCID: PMC2200545  PMID: 8809146

Abstract

A deregulated expression and/or release of large amounts of inflammatory cytokines such as IL-1 and TNF-α 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-1β release, and even inhibited LPS-induced IL-1β release. Induction of IL-1Ra by IgA could be detected both at the mRNA and protein levels in resting and activated monocytes. Ligation of FcαR 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 FcαR-mediated induction of tyrosine phosphorylation is required for the IgA-induced stimulation of IL-1Ra release. In addition, triggering of FcαR with MoAb specifically down-regulated TNF-α 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-1β, TNF-α and IL-6, interaction of IgA with human monocytes may actively contribute to the regulation of the inflammatory response.

Keywords: IgA, FcαR, IL-1Ra, proinflammatory cytokines, human monocytes

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