STREPTOCOCCAL-PYROGENIC-EXOTOXIN-A (SPE-A) SUPERANTIGEN INDUCED PRODUCTION OF HEMATOPOIETIC CYTOKINES, IL-12 AND IL-13 BY HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS

A quantitative and kinetic study of the release of the hematopoietic c ytokines IL-3, IL-5 and GM-CSF, the immunoregulatory cytokine IL-12 he terodimer (and its p40 subunit) and IL-13 by human peripheral blood mo nonuclear cells (PBMC) stimulated in vitro with the superantigen strep tococcal pyrogenic (erythrogenic) exotoxin A (SPE A) from Streptococcu s pyogenes is reported. PBMC were stimulated in parallel with heat-kil led group A streptococcal cells, E. coil lipopolysaccharide (LPS) and with concanavalin A (Con A) in certain experiments for comparative pur poses. 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 expressio n was induced by SPE A in a time-and dose-dependent manner in rather s ubstantial 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 st imulants induced relatively high amounts of GM-CSF. Interestingly, bot h 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 pr oduction in amounts comparable to those elicited by SPE A. The possibl e pathophysiological relevance of the elicitation by SPE A and strepto coccal cells of these cytokines is discussed. (C) 1997 Academic Press Limited.