title: Inhibition of IL-12 synthesis of peripheral blood mononuclear cells (PBMC) stimulated with a bacterial superantigen by pooled human immunoglobulin: implications for its effect on Kawasaki disease (KD).
abstract: The aim of this study was to further assess the role of pooled human immunoglobulin (PHIG) on cytokine production from PBMC stimulated with a bacterial superantigen. Human PBMC were cultured with Streptococcus pyrogenic exotoxin A (SPE-A) with or without PHIG and several proinflammatory cytokine levels of culture supernatants were measured. Serum cytokine levels of KD patients before and after PHIG therapy were also examined. PHIG greatly reduced the production of IL-12, interferon-gamma (IFN-gamma) and other cytokines from SPE-A-stimulated PBMC, while exogenous IL-12, but neither IL-1 nor tumour necrosis factor-alpha (TNF-alpha), restored IFN-gamma production inhibited by PHIG. Although PHIG partially adsorbed SPE-A, its inhibitory effect on cytokine production was not played by anti-SPE-A antibody. Although purified CD4+ T cells cultured with human HLA-DR-transfected mouse L cells and SPE-A could not effectively produce IFN-gamma, they produced large amounts of IFN-gamma if exogenous IL-12 was introduced. KD patients in the acute phase had higher levels of serum IFN-gamma than did controls and patients with bacterial infection. Although IL-12 levels of children with or without KD were not significantly different, IL-12 levels of children were much higher than those of adults. However, serum levels of IL-12 of KD patients were transiently but significantly decreased by PHIG therapy and IFN-gamma amounts subsequently reverted to basal levels thereafter. These findings indicate that PHIG inhibits IL-12 production of SPE-A-activated monocytes and thereby decreases IFN-gamma synthesis by T cells and suggest that inhibition of IL-12 and IFN-gamma production is an important part of the mechanisms underlying PHIG therapy on KD.
authors.affiliation: Department of Paediatrics, National Defence Medical College, Namiki, Tokorozawa, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Takata
authors.forename: S
authors.initials: S
authors.lastname: Seki
authors.forename: H
authors.initials: H
authors.lastname: Dobashi
authors.forename: S
authors.initials: S
authors.lastname: Takeshita
authors.forename: K
authors.initials: K
authors.lastname: Nakatani
authors.forename: Y
authors.initials: Y
authors.lastname: Kamezawa
authors.forename: H
authors.initials: H
authors.lastname: Hiraide
authors.forename: I
authors.initials: I
authors.lastname: Sekine
authors.forename: S
authors.initials: S
authors.lastname: Yoshioka
mesh_terms: D000327:Adsorption; D000818:Animals; D001426:Bacterial Proteins; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D005098:Exotoxins / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000494:pharmacology; D007739:L Cells; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D009080:Mucocutaneous Lymph Node Syndrome / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D001426:Bacterial Proteins; D005098:Exotoxins; D007136:Immunoglobulins; D007375:Interleukin-1; D008565:Membrane Proteins; C117980:SpeA protein, Streptococcus pyogenes; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C027951:erythrogenic toxin; D018664:Interleukin-12; D007371:Interferon-gamma