The Journal of infectious diseases
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Shock, a common and frequently fatal manifestation of gas gangrene caused by Clostridium perfringens, is probably mediated by extracellular toxins. Previous studies implicating alpha-toxin as the major lethal factor were frequently done with preparations contaminated with a second lethal factor, theta-toxin. We purified alpha- and theta-toxins from C. perfringens and demonstrated that both were lethal to mice. ⋯ Purified theta-toxin did not directly inhibit myocardial function. Shock induced by alpha-toxin may be partly mediated by direct depression of myocardial function. theta-Toxin reduced cardiac output in intact animals but had no direct effects on isolated heart preparations at concentrations that induced shock in intact animals. These data suggest that theta-toxin-induced shock could be mediated by an endogenous myocardial depressant factor.
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Two toxins, alpha (phospholipase C) and theta (oxygen-labile hemolysin), were purified from Clostridium perfringens type A and assayed for toxic effects on human polymorphonuclear leukocytes (PMNLs). Crude preparations containing both toxins totally inhibited chemotaxis and chemiluminescence responses of PMNLs and reduced PMNL viability. ⋯ Effects on chemotaxis were also dose dependent. Increased PMNL random migration was observed at a concentration of theta toxin of 0.06 HU per 2.5 X 10(5) PMNLs (P less than .05), whereas concentrations of greater than 0.08 HU per 2.5 X 10(5) PMNLs reduced both directed and random migration (P less than .05).
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Studies were conducted in guinea pigs, myelosuppressed by cyclophosphamide, for determination of whether passive immune therapy for Pseudomonas aeruginosa pneumonia would be useful in the setting of neutropenia. Groups of infected animals (14 per group) were treated with a single intravenous infusion of hyperimmune IgG antibody to P. aeruginosa (PA-IGIV; 500 mg/kg), tobramycin (1.7 mg/kg per 8 hr), ticarcillin (120 mg/kg per 6 hr), or combinations of these regimens. ⋯ Additive intrapulmonary killing of P. aeruginosa and prevention of bacteremia were observed in animals treated with tobramycin plus PA-IGIV compared with either treatment alone. Thus, passive immune therapy for P. aeruginosa pneumonia may be useful in the neutropenic host, but only when used in conjunction with antimicrobial agents.