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

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 micrograms/10(6) monocytes) or SLO (0.2-2.5 hemolytic units/10(6) monocytes), and production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta was measured at 24, 48, and 72 h. SPEA and SLO were potent inducers of TNF alpha, with maximum production occurring at 72 h for SPEA and at 48 h for SLO (1067 and 687 pg/ml, respectively). In contrast, IL-1 beta production was greater for SLO than for SPEA (557 vs. 258 pg/ml). In addition, the effects of SPEA and SLO together were synergistic in terms of monocyte IL-1 beta production: SPEA, 193 pg/ml; SLO, 452 pg/ml; SPEA plus SLO, 799 pg/ml. These findings suggest TNF alpha and IL-1 beta are important candidates for mediating shock in severe streptococcal infections.