title: Endotoxin tolerance: effects on lethality and macrophage thromboxane (B2) and interleukin 6 production.
abstract: The effects of endotoxin pretreatment on induction of in vivo tolerance to endotoxin lethality, and on in vitro stimulated peritoneal macrophage mediators, thromboxane (TX)B2 and interleukin 6 (IL-6) were investigated. Rats were given i.p. injections of S. enteritidis endotoxin on days 1 (100 micrograms/kg) and 2 (500 micrograms/kg), respectively. After 5 days, or after 2-8 weeks of initial pretreatment, either endotoxin-induced mortality was assessed, or peritoneal cells were harvested for the in vitro studies. Endotoxin tolerant rats were resistant (p < .05) to endotoxin lethality for 2 weeks after initial induction of tolerance. In vitro studies with peritoneal macrophages demonstrated that endotoxin or monophosphoryl lipid A stimulated (p < .05) TXB2 production. However, peritoneal cells harvested from endotoxin tolerant rats exhibited suppressed (*p < .05) TXB2 production to both stimuli which persisted for at least 8 weeks. Endotoxin stimulated (p < .05) in vitro levels of IL-6 in control cells, but in contrast to the suppressed TXB2 production in tolerance, also stimulated (p < .05) in vitro IL-6 in the endotoxin tolerant group. Paradoxically, lipid A did not induce IL-6 production in either group. These composite observations suggest that during endotoxin tolerance neither in vitro peritoneal macrophage TXB2 nor IL-6 synthesis temporally correlate with in vivo resistance to lethality.
authors.affiliation: Department of Physiology, Medical University of South Carolina, Charleston 29425, USA.
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.forename: P V
authors.initials: PV
authors.lastname: Halushka
authors.forename: J A
authors.initials: JA
authors.lastname: Cook
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004361:Drug Tolerance; D015850:Interleukin-6 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010537:Peritoneum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D012481:Salmonella Infections, Animal / Q000378:metabolism / Q000473:pathology; D012772:Shock, Septic / Q000378:metabolism* / Q000473:pathology; D013929:Thromboxane B2 / Q000096:biosynthesis*
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D013929:Thromboxane B2