title: Immunomodulatory properties of human serum immunoglobulin A: anti-inflammatory and pro-inflammatory activities in human monocytes and peripheral blood mononuclear cells.
abstract: Our study investigated the immunomodulatory activities of human plasma-derived serum immunoglobulin (Ig)A. Previous findings seem contradictory indicating either pro- or anti-inflammatory activities. We used serum IgA purified from large plasma pools and studied the modulation of the release of cytokines and chemokines from resting and lipopolysaccharide (LPS, endotoxin)-stimulated human adherent monocytes and human peripheral blood mononuclear cells (PBMC). Our results indicate that IgA down-modulates the release of the pro-inflammatory chemokines monocyte chemoattractant protein (MCP) 1, macrophage inflammatory protein (MIP) 1alpha and MIP1beta from LPS-stimulated PBMC and the release of MCP1, MIP1alpha and MIP1beta from LPS-stimulated monocytes. Furthermore, we confirmed previous reports that plasma-derived serum IgA down-modulates the release of the pro-inflammatory cytokines, interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha, from LPS-stimulated monocytes and PBMC, and up-regulates the release of IL-1 receptor antagonist (IL-1RA) from resting and LPS-stimulated monocytes and resting PBMC. This IgA-mediated up-regulation of IL-1RA is independent of the simultaneous up-regulation of IL-1beta release, as shown by blocking the biological activity of IL-1beta with a neutralizing antibody. On the other hand, we also found an IgA-induced pro-inflammatory activity, namely IgA-mediated up-regulation of the release of pro-inflammatory IL-1beta as well as down-regulation of the anti-inflammatory cytokines IL-10 and IL-12p40 from LPS-stimulated monocytes and PBMC and a down-regulation of transforming growth factor (TGF)-beta from resting and LPS-stimulated PBMC. We conclude that human serum IgA has both an anti-inflammatory and a pro-inflammatory capacity and this dual capacity might contribute to the feedback mechanisms maintaining a balance between pro-inflammatory and anti-inflammatory activities.
authors.affiliation: Baxter BioScience, Vienna, Austria.
authors.forename: K
authors.initials: K
authors.lastname: Olas
authors.forename: H
authors.initials: H
authors.lastname: Butterweck
authors.forename: W
authors.initials: W
authors.lastname: Teschner
authors.forename: H P
authors.initials: HP
authors.lastname: Schwarz
authors.forename: B
authors.initials: B
authors.lastname: Reipert
mesh_terms: D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000276:immunology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016207:Cytokines / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology*; D007375:Interleukin-1 / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D019402:Macrophage Inflammatory Proteins / Q000276:immunology; D009000:Monocytes / Q000276:immunology; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D016212:Transforming Growth Factor beta / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D016207:Cytokines; D007070:Immunoglobulin A; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D017472:Receptors, Interleukin-1; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12