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

• Published in: Clinical and experimental immunology Vol. 105; no. 3; pp. 537 - 543
• Main Authors: WOLF, H. M., HAUBER, I., GULLE, H., SAMSTAG, A., FISCHER, M. B., AHMAD, R. U., EIBL, M. M.
• Format: Journal Article
• Language: English
• Published: Oxford BSL Blackwell Science Ltd 01.09.1996; Blackwell; Blackwell Science Inc
• Subjects: Adult; Antigens, CD - drug effects; Antigens, CD - physiology; Biological and medical sciences; Down-Regulation - immunology; FcαR; Fundamental and applied biological sciences. Psychology; Fundamental immunology; human monocytes; Humans; IgA; IL‐1Ra; Immunobiology; Immunoglobulin A - blood; Immunoglobulin A - pharmacology; Inflammation Mediators - blood; Inflammation Mediators - pharmacology; Interleukin 1 Receptor Antagonist Protein; Interleukin-1 - biosynthesis; Interleukin-6 - biosynthesis; Modulation of the immune response (stimulation, suppression); Monocytes - immunology; Monocytes - metabolism; Original; Phosphorylation; proinflammatory cytokines; Protein-Tyrosine Kinases - metabolism; Receptors, Fc - drug effects; Receptors, Fc - physiology; Receptors, Interleukin-1 - antagonists & inhibitors; Sialoglycoproteins - biosynthesis; Tumor Necrosis Factor-alpha - biosynthesis; Human; IgA; Immune response; Monocyte; Cytokine; Biosynthesis; Inflammation; Biological activity; Mechanism; Interleukin 6; Immunosuppression; Fc-Fragment; Interleukin 1; Tumor necrosis factor α; Biological receptor
• ISSN: 0009-9104; 1365-2249
• 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‐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.