thromboxane-b2 and Salmonella-Infections--Animal

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.

Topics: Animals; Cells, Cultured; Disease Models, Animal; Drug Tolerance; Interleukin-6; Lipopolysaccharides; Macrophages; Male; Peritoneum; Rats; Salmonella Infections, Animal; Shock, Septic; Thromboxane B2

Salmonella-associated arthritis of rats was used as an experimental model for in vivo evaluation of prostaglandins in chronic inflammation. Since the arthritic lesions were localized mainly in the hind paws, femorla vein plasma measurements of prostaglandins were made to estimate the amounts of PGE1, PGE2 alpha, 6-keto-PGF1 alpha and TXB2 produced during the progression of the arthritic disease. PGE1 production was significantly increased in the early phase of infection but these changes were inversely related to the joint swelling in the later stages of the disease. Changes in products of arachidonic acid (20:4 omega 6) were opposite to those observed in PGE1, a product of dihomo-gamma-linolenic acid, (20:3 omega 6), in that measurable levels of these chemicals were lower in the early phase of infection but there was a progressive increase in each compound during the chronic phase of inflammation. Concentrations of PGE2, PGF2 alpha, 6-keto-PGF1 alpha and TXB2 increased proportionately to the severity of the arthritic lesion.

Topics: 6-Ketoprostaglandin F1 alpha; Alprostadil; Animals; Arthritis, Infectious; Dinoprost; Dinoprostone; Femoral Vein; Hindlimb; Male; Prostaglandins; Prostaglandins E; Prostaglandins F; Rats; Salmonella enteritidis; Salmonella Infections, Animal; Thromboxane B2