Lymphokine production induced by streptococcal pyrogenic exotoxin‐A is selectively down‐regulated by pooled human IgG

Abstract
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)‐1α, IL‐1β, IL‐1ra, IL‐6, IL‐8, IL‐2, tumor necrosis factor interferon(IFN)‐γ and TNF‐α and TNF‐β 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‐γ and TNF‐β 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‐γ and TNF‐β. These results indicate an immunomodulatory potential by IVIg on streptococcally induced T cell activation and lymphokine production.