Endotoxin is not an essential mediator in toxic shock syndrome

Abstract

The hypothesis that toxic shock syndrome toxin 1 (TSST-1) exerts its deleterious effects in toxic shock syndrome (TSS) primarily by enhancing the lethality of small amounts of endogenous endotoxin derived from mucosal colonization with gram-negative bacteria was assessed by evaluating two means of inactivating endotoxin in rabbit models of TSS. In both of these models, toxins and TSST-1 are allowed to diffuse constantly from a subcutaneous depot. Immunologic inactivation of endotoxin with antiserum to the core lipopolysaccharide did not change the clinical course or mortality among animals infected with live TSS-associated staphylococci or among animals with a subcutaneous depot of TSST-1. Anti-TSST-1 was successful in preventing disease and death in these models. Pharmacologic inactivation of endotoxin by pretreatment or continuous treatment with polymyxin B did not prevent illness or mortality in the toxin depot model. Endotoxin thus appears not to be an essential mediator in TSS, since TSS-like illness develops and progresses despite inactivation of endotoxin in animal model systems that are faithful both physiologically and clinically to TSS in humans.