title: 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.
authors.affiliation: Department of Pediatrics, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu 96826.
authors.forename: M E
authors.initials: ME
authors.lastname: Melish
authors.forename: S
authors.initials: S
authors.lastname: Murata
authors.forename: C
authors.initials: C
authors.lastname: Fukunaga
authors.forename: K
authors.initials: K
authors.lastname: Frogner
authors.forename: S
authors.initials: S
authors.lastname: Hirata
authors.forename: C
authors.initials: C
authors.lastname: Wong
mesh_terms: D000818:Animals; D001427:Bacterial Toxins; D004195:Disease Models, Animal; D004731:Endotoxins / Q000633:toxicity*; D004768:Enterotoxins / Q000493:pharmacokinetics / Q000633:toxicity*; D011112:Polymyxin B / Q000627:therapeutic use; D011817:Rabbits; D012772:Shock, Septic / Q000188:drug therapy / Q000209:etiology*; D013211:Staphylococcus aureus / Q000502:physiology*; D018089:Superantigens
chemical_list: D001427:Bacterial Toxins; D004731:Endotoxins; D004768:Enterotoxins; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; D011112:Polymyxin B