title: Streptococcal toxic shock syndrome: synthesis of tumor necrosis factor and interleukin-1 by monocytes stimulated with pyrogenic exotoxin A and streptolysin O.
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 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.
authors.affiliation: University of Idaho, Moscow.
authors.forename: S P
authors.initials: SP
authors.lastname: Hackett
authors.forename: D L
authors.initials: DL
authors.lastname: Stevens
mesh_terms: D001426:Bacterial Proteins; D002478:Cells, Cultured; D005098:Exotoxins / Q000276:immunology*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D008565:Membrane Proteins; D009000:Monocytes / Q000276:immunology*; D011749:Pyrogens / Q000276:immunology; D013297:Streptococcus pyogenes; D013301:Streptolysins / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D001426:Bacterial Proteins; D005098:Exotoxins; D007375:Interleukin-1; D008565:Membrane Proteins; D011749:Pyrogens; C117980:SpeA protein, Streptococcus pyogenes; D013301:Streptolysins; D014409:Tumor Necrosis Factor-alpha; C027951:erythrogenic toxin; C025964:streptolysin O