COMPARATIVE-STUDY OF CYTOKINE RELEASE BY HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS STIMULATED WITH STREPTOCOCCUS-PYOGENES SUPERANTIGENIC ERYTHROGENIC TOXINS, HEAT-KILLED STREPTOCOCCI, AND LIPOPOLYSACCHARIDE

The differences between toxic or septic shocks in humans during infect ions by streptococci and gramnegative bacteria remain to be fully char acterized. For this purpose, a quantitative study of the cytokine-indu cing capacity of Streptococcus pyogenes erythrogenic (pyrogenic) exoto xins (ETs) A and C, heat-killed S. pyogenes bacteria, and Neisseria me ningitidis endotoxin (lipopolysaccharide [LPS]) on human peripheral bl ood mononuclear cells (PBMC) and monocytes has been undertaken. The le vels of interleukin-1 alpha. (IL-1 alpha), IL 1 beta; IL-6, IL-8, tumo r necrosis factor alpha (TNP-alpha), and TNF-beta induced by these bac terial products and bacteria were determined by using cell supernatant s. The capacity of ETs to elicit the monocyte-derived cytokines IL-1 a lpha, IL-1 beta, IL-6, and TNF-alpha was found to depend on the presen ce of T lymphocytes, because of the failure of purified monocytes to p roduce significant amounts of these cytokines in response to ETs. PBMC elicited large amounts of these cytokines, as well as IL-8 and TNF-be ta, with an optimal release after 48 to 96 h. The most abundant cytoki ne produced in response to ETA was IL-8. In contrast to the superantig ens ETA and ETC, LPS and heat-killed streptococci stimulated the produ ction of significant amounts of IL-1 alpha, IL-1 beta, IL-6, and TNF-a lpha, with optimal production after 24 to 48 h in monocytes, indicatin g no significant involvement of T cells in the process. ETs, but neith er LPS nor streptococci, were potent inducers of TNF-beta in PBMC. Thi s study outlines the differences in the pathophysiological features of shock evoked by endotoxins and superantigens during infection by gram -negative bacteria and group A streptococci, respectively. The product ion of TNF-alpha was a common pathway for LPS, streptococcal cells, an d ETs, although cell requirements and kinetics of cytokine release wer e different.