Human serum IgA downregulates the release of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6) in human monocytes.
While the protective effect of IgA antibodies against infection of the mucosal surfaces is well documented, the mechanisms involved are not entirely clear. The aim of the current study is to investigate the effect of human serum IgA on the release of inflammatory cytokines in human monocytes activated with a particulate stimulus, Haemophilus influenzae type b (Hib), or soluble lipopolysaccharide (LPS) purified from Escherichia coli. Our results show that IgA downregulates tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) production, whereas IgG examined in parallel had no effect. IgA had no inhibitory effect on Hib-induced granulocyte-macrophage colony-stimulating factor release. TNF-alpha and IL-6 release were downmodulated if IgA was present during cytokine induction, and IgA was also inhibitory if added to Hib-pretreated monocytes during the phase of cytokine release. These findings indicate that there are at least two mechanisms whereby IgA antibodies can downregulate TNF-alpha and IL-6 release in human monocytes: by a mechanism acting during the time of monocyte activation, and a mechanism that downregulates the production and/or the release of these cytokines in activated monocytes. Regulation of TNF-alpha and IL-6 release by IgA may be among the antiinflammatory mechanisms preventing an uncontrolled release of potentially noxious levels of inflammatory cytokines during acute and/or chronic inflammation.
Wolf
H M
HM
Institute of Immunology, University of Vienna, Austria.
Fischer
M B
MB
Pühringer
H
H
Samstag
A
A
Vogel
E
E
Eibl
M M
MM
D000938:Antigen-Presenting Cells / Q000276:immunology; D002470:Cell Survival; D002473:Cell Wall / Q000276:immunology; D002478:Cells, Cultured; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006193:Haemophilus influenzae / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood* / Q000494:pharmacology; D007074:Immunoglobulin G / Q000494:pharmacology; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C034639:polymeric IgA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor