title: Staphylococcus epidermidis induces complement activation, tumor necrosis factor and interleukin-1, a shock-like state and tissue injury in rabbits without endotoxemia. Comparison to Escherichia coli.
abstract: Tumor necrosis factor (TNF) and IL-1 are thought to mediate many of the pathophysiologic changes of endotoxemia and Gram-negative bacteremia. In these studies, heat-killed Staphylococcus epidermidis were infused into rabbits to determine whether an endotoxin (LPS)-free microorganism also elicits cytokinemia and the physiologic abnormalities seen in Gram-negative bacteremia. S. epidermidis induced complement activation, circulating TNF and IL-1, and hypotension to the same degree as did one-twentieth the number of heat-killed Escherichia coli. Circulating IL-1 beta levels had a greater correlation coefficient (r = 0.81, P less than 0.001) with the degree of hypotension than TNF levels (r = 0.48, P less than 0.02). Leukopenia, thrombocytopenia, diffuse pulmonary capillary aggregation of neutrophils, and hepatic necrosis with neutrophil infiltration were observed to the same extent after either S. epidermidis or E. coli infusion. However, S. epidermidis infusion did not induce significant (less than 60 pg/ml) endotoxemia, whereas E. coli infusion resulted in high (11,000 pg/ml) serum endotoxin levels. S. epidermidis, E. coli, LPS, or S. epidermidis-derived lipoteichoic acid (LTA) induced TNF and IL-1 from blood mononuclear cells in vitro. E. coli organisms and LPS were at least 100-fold more potent than S. epidermidis or LTA. Thus, a shock-like state with similar levels of complement activation as well as circulating levels of IL-1 and TNF were observed following either S. epidermidis or E. coli. These data provide further evidence that host factors such as IL-1 and TNF are common mediators of the septic shock syndrome regardless of the organism.
authors.affiliation: Department of Medicine, Tufts University, Boston, Massachusetts.
authors.forename: G
authors.initials: G
authors.lastname: Wakabayashi
authors.forename: J A
authors.initials: JA
authors.lastname: Gelfand
authors.forename: W K
authors.initials: WK
authors.lastname: Jung
authors.forename: R J
authors.initials: RJ
authors.lastname: Connolly
authors.forename: J F
authors.initials: JF
authors.lastname: Burke
authors.forename: C A
authors.initials: CA
authors.lastname: Dinarello
mesh_terms: D000818:Animals; D003167:Complement Activation; D004926:Escherichia coli / Q000276:immunology / Q000472:pathogenicity; D006439:Hemodynamics; D007375:Interleukin-1 / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008070:Lipopolysaccharides / Q000097:blood / Q000494:pharmacology; D008107:Liver Diseases / Q000382:microbiology / Q000473:pathology; D009336:Necrosis; D011817:Rabbits; D012769:Shock / Q000382:microbiology*; D013212:Staphylococcus epidermidis / Q000276:immunology* / Q000472:pathogenicity; D013682:Teichoic Acids / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D007375:Interleukin-1; D008070:Lipopolysaccharides; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; C009900:lipoteichoic acid