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 (IV Ig) on cytokine production induced by streptococcal pyrogenic exotoxin -A (SPE-A) was studied at the single-cell level using cytokine-specifi c monoclonal antibodies and indirect immunofluorescence or immunohisto chemical staining. Mononuclear cells from healthy adult blood donors w ere stimulated with SPE-A alone or in the presence of IVIg. IVIg was a dded either prior to stimulation or 24 h after initiation of cultures, in an attempt to evaluate whether IVIg treatment could influence an a lready established systemic streptococcal disease. Cells were harveste d 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 n ecrosis factor interferon(LFN)-gamma and TNF-alpha and TNF-beta and gr anulocyte macrophage-colony-stimulating factor. Stimulation with SPE-A lead to extensive lymphokine and monokine production. With the additi on of IVIg prior to stimulation there was a strong reduction of blast transformation and an almost complete inhibition of lymphokine product ion, in particular in the synthesis of IFN-gamma and TNF-beta while th e synthesis of IL-1 and IL-8 was either unaffected or increased. Addin g IVIg 24 h after SPE-A stimulation also resulted in reduced blast tra nsformation and decreased synthesis of IFN-gamma, and TNF-beta. These results indicate an immunomodulatory potential by IVIg on streptococca lly induced T cell activation and lymphokine production.