THE PATHOGENESIS OF EXPERIMENTAL TOXIC SHOCK SYNDROMEcolon; THE ROLE OF INTERLEUKIN-2 IN THE INDUCTION OF HYPOTENSION AND RELEASE OF CYTOKINES

摘要

Toxic shock syndrome (TSS) is a multisystem disorder characterized by fever, hypotension, and involvement of three other organ systems. The etiologic agent is a toxigenic strain ofStaphylococcus aureuswhich secretes the exotoxin, TSST-1. The toxin is a superantigen which stimulates the immune system to produce interleukin-1 (IL-1), interleukin-2, and tumor necrosis factor (TNF). We hypothesized that TSST-1 induces the release of IL-2 which in turn is either directly involved or acts via an additional mediator to produce hypotension. We submitted four pairs of normal anesthetized adult female baboons to intravenous boluses of TSST-1. One baboon in each pair received anti-IL-2 intravenously and anti-IL-2 receptor intrathyroidally 15 min prior to TSST-1. The other baboon received the same dose and placement of anti-sheep red blood cell antibody. Systolic and diastolic blood pressure was recorded continuously and mean arterial pressure was calculated and plotted. IL-1, IL-2, IL-6, and TNF were measured in serum at varying times before and after toxin administration. Systolic, diastolic, and mean arterial pressure were significantly lower in the sham-treated group versus the experimental (anti-IL-2/IL-2R) group (p .05 for all variables). In addition no differences were seen in any of the measurements between experimentally treated baboons and those receiving no TSST-1. Abrogation of the IL-2 response with the antibodies led to the lower production of IL-1, TNF, and IL-6 with statistically significant differences (p .05) at 1, 2, 3, 4, and 8 h following TSST-1 administration for IL-2, at 1 and 4 h for IL-1, and at 2 h for IL-6. We conclude that the cytokine IL-2 is an important host mediator involved in the pathogenesis of TSS.