Role of prostaglandin-mediated mechanisms during experimentally induced endotoxin fever in the lactating goat.
The effects of endotoxin (LPS) on the cortisol, glucose, NEFA (non-esterified fatty acids), STH (somatotropin) and oxytocin levels in plasma of goats are described. The changes in plasma cortisol, STH and NEFA, as well as in RT (rectal temperature) were compared after i.v. and i.mam. administration of endotoxin. The other parameters, glucose and oxytocin, were followed only after i.v. endotoxin administration. The observed metabolic and hormonal alterations in plasma were also studied after pretreating the goats with the non-steroidal anti-inflammatory and antipyretic drug flurbiprofen in order to evaluate the possible involvement of prostaglandin in these phenomena. After i.v. administration of LPS a biphasic temperature curve for the highest dose of LPS with peak maxima at 1h and 4h after LPS challenge, was observed. Intramammary administration of endotoxin induces a monophasic fever response, with a latency time of approximately 3h, and peak values after 6h. The onset of the fever response in the i.v. experiments coincided with the oxytocin maximum and with early hyperglycemia. Intravenous endotoxin in goats also induces an increase in plasma NEFA, cortisol and STH. The early increase in NEFA, with a maximum after 2h and occurring before the fever peak, is followed by a significant rise in cortisol with peak effects after 3 h. The increase in plasma STH coincided with the decrease in plasma NEFA returning to control levels again. Peak concentrations in plasma STH occurred after 4 h. All the changes observed after the i.v. administration of endotoxin are dose-dependent. Pretreating goats with flurbiprofen completely abolished fever response, as well as the early hyperglycemia and the oxytocin release to i.v. LPS, indicating that these changes were prostaglandin-mediated and might be a reflexion of an activation of the sympathetic adrenomedullary system. The LPS-induced changes in plasma cortisol, NEFA and STH are only partly depressed and delayed by flurbiprofen. The residual hormonal responses to high doses of endotoxin suggest that an additional direct action of circulating endotoxins on the hypothalamus cannot be excluded. Intramammary LPS administration in goats only induced a very weak increase in plasma cortisol. The complex interplay of hormones and metabolic substances in the homeostasis of the inflammation reaction is discussed.
Faculty of Veterinary Medicine, Department of Veterinary Physiology, University of Ghent.
A M
AM
Massart-Leen
G
G
Vandeputte-Van Messom
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005334:Fever / Q000097:blood; D006041:Goats; D013006:Growth Hormone / Q000097:blood; D006854:Hydrocortisone / Q000097:blood; D007774:Lactation; D010121:Oxytocin / Q000097:blood; D011453:Prostaglandins / Q000378:metabolism; D014115:Toxemia / Q000097:blood*
D001786:Blood Glucose; D004731:Endotoxins; D005230:Fatty Acids, Nonesterified; D011453:Prostaglandins; D010121:Oxytocin; D013006:Growth Hormone; D006854:Hydrocortisone