SIMILAR CYTOKINE INDUCTION PROFILES OF A NOVEL STREPTOCOCCAL EXOTOXIN, MF, AND PYROGENIC EXOTOXIN-A AND EXOTOXIN-B

The cytokine production induced by a newly discovered streptococcal ex otoxin, MF, and the pyrogenic exotoxins SpeA and SpeB was determined b y in vitro stimulation of peripheral blood mononuclear cells (PBMCs) o btained from healthy blood donors. The induction and kinetics of inter leukin-1 alpha (IL-1 alpha), IL-1 beta, IL-1 receptor antagonist, IL-2 , IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, gamma interferon, tumor necrosi s factor alpha (TNF-alpha), TNF-beta, and granulocyte-macrophage colon y-stimulating factor were studied at the single-cell level by use of c ytokine-specific monoclonal antibodies and intracellular immunofluores cent juxtanuclear staining. The cytokine-producing cells with the exce ption of IL-1-expressing cells, had a characteristic morphology genera ted by the accumulation of cytokines in the Golgi organelle. MF, SpeA, and SpeB induced a massive gamma interferon and TNF-beta response in 10 to 16% of the PBMCs after 48 to 96 h of cell stimulation. In contra st, IL-2 and TNF-alpha production was detected in only 1 to 3% of the PBMCs. The induction of a lymphocyte TH2 phenotype response, including production of IL-3, IL-4, IL-5, and IL-10, was weak However, the mono kines, IL-1 alpha, IL-1 beta, IL-1 receptor antagonist, and IL-8, were consistently found and gradually produced, peaking at 24 h in approxi mately 5 to 8% of the PBMCs. MF showed extensive cytokine-and prolifer ation-inducing capacities equal to those of SpeA and SpeB, which sugge sts that MF is also a superantigen. A marked interindividual variation could be noted both in the proliferative response and in the cytokine induction of lymphocytes isolated from different individuals, which m ay be one explanation for the varying clinical severity noticed during group A streptococcal infections.