Streptococcal Toxic Shock Syndrome: Synthesis of Tumor Necrosis Factor and Interleukin-1 by Monocytes Stimulated with Pyrogenic Exotoxin A and Streptolysin O

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Abstract
Previous studies have found that 80% of strains isolated from patients with the streptococcal toxic shock syndrome produce pyrogenic exotoxin A (SPEA) and 100% produced streptolysin O (SLO). To elucidate the cellular mechanisms contributing to shock, human monocytes were stimulated with SPEA (0.1–10 µ,/l06 monocytes) or SLO (0.2–2.5 hemolytic units/106 monocytes), and production of tumor necrosis factor (TNF)-α and interleukin (IL)-Iβ was measured at 24, 48, and 72 h. SPEA and SLO were potent inducers of TNFα, with maximum production occurring at 72 h for SPEA and at 48 h for SLO (1067 and 687 pg/ml, respectively). In contrast, IL-1β production was greater for SLO than for SPEA (557 vs. 258 pgjml). In addition, the effects of SPEA and SLO together were synergistic in terms of monocyte IL-lβ production: SPEA, 193 pgjml; SLO, 452 pgjml; SPEA plus SLO, 799 pgjml. These findings suggest TNFα and IL-1β are important candidates for mediating shock in severe streptococcal infections.

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