title: Ibuprofen prevents Pasteurella hemolytica endotoxin-induced changes in plasma prostanoids and serotonin, and fever in sheep.
abstract: Intravenous infusion of Pasteurella hemolytica endotoxin caused marked increases in the plasma levels of thromboxane B2 (TxB2), prostaglandins (PG) and serotonin in sheep. The control values for TxB2, 6-keto-PGF1 alpha, PGF2 alpha, and serotonin before endotoxin infusion averaged 283 +/- 53 (standard error of mean), 281 +/- 14 and 199 +/- 27 pg/ml and 57 +/- 3 ng/ml, respectively. At 50 min during endotoxin infusion, these values were increased to their maximum of 376, 339, 325 and 202% of control, respectively. Body temperature increased from the control value of 39.5 +/- 0.1 degrees C to a maximum of 41.5 +/- 0.1 degrees C at 200-300 min of infusion. In the second part of this study, we have examined the effects of ibuprofen on endotoxin-induced increases in plasma PG, TxB2, and serotonin levels and body temperature. The control values for TxB2, 6-keto-PGF1 alpha, PGF2 alpha, and temperature prior to ibuprofen and endotoxin infusion averaged 238 +/- 35, 335 +/- 44 and 248 +/- 28 pg/ml, 65 +/- 3 ng/ml and 40.1 +/- 0.2 degrees C, respectively. A loading dose (15 mg/kg) of ibuprofen was followed by infusion of endotoxin (12 micrograms/kg) and ibuprofen (43.3 mg/kg) over 500 min. Plasma levels of 6-keto-PGF1 alpha and serotonin increased only to 131 and 149% of control at 50 min of infusion, and levels of PGF2 alpha and TxB2 decreased to 50 and 80% of control at 100 and 150 min of infusion, respectively. Temperature remained unchanged. Ibuprofen effectively suppressed endotoxin-induced increases in the plasma levels of TxB2, 6-keto-PGF1 alpha, PGF2 alpha, and serotonin and body temperature. It was concluded from the present study that nonsteroidal anti-inflammatory drugs as an adjunct to antibiotic therapy might have a rational basis in treatment of endotoxin toxicity.
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D015237:Dinoprost; D004731:Endotoxins / Q000633:toxicity*; D005260:Female; D005334:Fever / Q000139:chemically induced / Q000662:veterinary*; D007052:Ibuprofen / Q000494:pharmacology*; D010325:Pasteurella / Q000378:metabolism*; D010326:Pasteurella Infections / Q000662:veterinary*; D011453:Prostaglandins / Q000097:blood*; D011460:Prostaglandins F / Q000097:blood; D012701:Serotonin / Q000097:blood*; D012756:Sheep; D012757:Sheep Diseases / Q000097:blood / Q000209:etiology; D013929:Thromboxane B2 / Q000097:blood; D013931:Thromboxanes / Q000097:blood*
chemical_list: D004731:Endotoxins; D011453:Prostaglandins; D011460:Prostaglandins F; D013931:Thromboxanes; D012701:Serotonin; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D015237:Dinoprost; D007052:Ibuprofen