Streptococcal pyrogenic exotoxin A (SPE A) superantigen induced production of hematopoietic cytokines, IL-12 and IL-13 by human peripheral blood mononuclear cells.

ABSTRACT

A quantitative and kinetic study of the release of the hematopoietic cytokines IL-3, IL-5 and GM-CSF, the immunoregulatory cytokine IL-12 heterodimer (and its p40 subunit) and IL-13 by human peripheral blood mononuclear cells (PBMC) stimulated in vitro with the superantigen streptococcal pyrogenic (erythrogenic) exotoxin A (SPE A) from Streptococcus pyogenes is reported. PBMC were stimulated in parallel with heat-killed group A streptococcal cells, E. coli lipopolysaccharide (LPS) and with concanavalin A (Con A) in certain experiments for comparative purposes. The cytokines were assayed in the supernatant fluids by ELISA. IL-13 expression was also determined by a quantitative competitive PCR. IL-3, IL-5, GM-CSF, IL-12 p40, IL-12 heterodimer and IL-13 expression was induced by SPE A in a time- and dose-dependent manner in rather substantial amounts except the IL-12 heterodimer, which was released in small quantities. In contrast to SPE A, IL-3, IL-5 and IL-13 were not or poorly elicited by streptococcal cells or LPS whereas these two stimulants induced relatively high amounts of GM-CSF. Interestingly, both IL-12 p40 and IL-12 heterodimer were released in much higher amounts by streptococcal cells. Con A induced IL-3, IL-5, GM-CSF and IL-13 production in amounts comparable to those elicited by SPE A. The possible pathophysiological relevance of the elicitation by SPE A and streptococcal cells of these cytokines is discussed.