Lymphokine production induced by streptococcal pyrogenic exotoxin-A is selectively down-regulated by pooled human IgG.
The influence of pooled human IgG preparations for intravenous use (IVIg) on cytokine production induced by streptococcal pyrogenic exotoxin-A (SPE-A) was studied at the single-cell level using cytokine-specific monoclonal antibodies and indirect immunofluorescence or immunohistochemical staining. Mononuclear cells from healthy adult blood donors were stimulated with SPE-A alone or in the presence of IVIg. IVIg was added either prior to stimulation or 24 h after initiation of cultures, in an attempt to evaluate whether IVIg treatment could influence an already established systemic streptococcal disease. Cells were harvested after 48 or 72 h of culture and stained for the following cytokines: interleukin(IL)-1 alpha, IL-1 beta, IL-1ra, IL-6, IL-8, IL-2, tumor necrosis factor interferon(IFN)-gamma and TNF-alpha and TNF-beta and granulocyte macrophage-colony-stimulating factor. Stimulation with SPE-A lead to extensive lymphokine and monokine production. With the addition of IVIg prior to stimulation there was a strong reduction of blast transformation and an almost complete inhibition of lymphokine production, in particular in the synthesis of IFN-gamma and TNF-beta while the synthesis of IL-1 and IL-8 was either unaffected or increased. Adding IVIg 24 h after SPE-A stimulation also resulted in reduced blast transformation and decreased synthesis of IFN-gamma and TNF-beta. These results indicate an immunomodulatory potential by IVIg on streptococcally induced T cell activation and lymphokine production.
Skansén-Saphir
U
U
Department of Immunology, Arrhenius Laboratories for Natural Sciences, Stockholm University, Sweden.
Andersson
J
J
Björk
L
L
Andersson
U
U
D000328:Adult; D001426:Bacterial Proteins; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D015536:Down-Regulation; D005098:Exotoxins / Q000276:immunology*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008233:Lymphotoxin-alpha / Q000096:biosynthesis; D008565:Membrane Proteins; D013291:Streptococcus / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*
D001426:Bacterial Proteins; D016207:Cytokines; D005098:Exotoxins; D016756:Immunoglobulins, Intravenous; D008233:Lymphotoxin-alpha; D008565:Membrane Proteins; C117980:SpeA protein, Streptococcus pyogenes; D018089:Superantigens; C027951:erythrogenic toxin; D007371:Interferon-gamma