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Title: DECREASED RESPONSE TO ENDOTOXIN CHALLENGE BY PRE-TREATMENT WITH ERGOTAMINE

Author
item FILIPOV, N - UNIVERSITY OF GEORGIA
item THOMPSON, F - UNIVERSITY OF GEORGIA
item Stuedemann, John
item DAWE, D - UNIVERSITY OF GEORGIA
item Elsasser, Theodore
item Kahl, Stanislaw
item Young, Colin

Submitted to: Society of Toxicology
Publication Type: Abstract Only
Publication Acceptance Date: 1/15/1999
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: The objective of this experiment was to investigate whether the ergot alkaloid, ergotamine (ET), an alkaloid used to model fescue toxicosis in cattle, increases the response of cattle to endotoxin (LPS) challenge. Steers (n=16) were divided into the following groups: control (C), ergotamine (ET), endotoxin (LPS), and ET=LPS. ET and ET+LPS groups received a single bolus i. v. injection of ET (40 ug/kg/BW), whereas C and LPS steers received a single bolus injection of sterile vehicle. Thirty minutes after ET/vehicle administration, a single bolus i. v. injection of LPS (0.2 ug/kg/BW) was given. Blood was collected at various time points for 48 h post LPS. Endotoxin alone increased the circulating levels of tumor necrosis factor alpha (TNF-alpha), cortisol, the acute-phase protein haptoglobin (Hp), thromboxane B2 (TXB2), and rectal temperature (RT), and decreased plasma glucose and insulin-like growth factor-1 (IGF-1). Importantly, haptoglobin, TNF-alpha, and TXB2 increases were blunted by pretreatment with ET compared to LPS. The combination ET+LPS resulted in hyperglycemia followed by profound hypoglycemia. Ergotamine alone, increased RT, plasma urea nitrogen, packed cell volume and glucose and decreased serum prolactin (PRL). Therefore, administration of LPS to steers resulted in a typical metabolic and endocrine response. The combination of ET+LPS attenuated major effects of LPS alone. Thus, acute administration of ET appeared to be antinflammatory as it decreased the inflammatory response to LPS.