|Kahl, Stanislaw - Stass|
Submitted to: American Society for Experimental Biology and Medicine Proceedings
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/14/2000
Publication Date: N/A
Interpretive Summary: Toxins in grasses infected with some molds and fungi cause diseases in cattle that result in reproductive failure, poor growth and a decreased resistance to infection. Some of the toxins made by the mold when it infects grasses like fescue have properties that boost the inflammatory response of cattle to infection. We studied how an analog of these toxins might be used to improve the disease response of cattle if challenged with this mold toxin. When we administered the drug ergotamine to cattle prior to giving a simulated infection, the ergotamine was successful in decreasing the severity of the inflammatory response. This data suggests that ergot drugs like ergotamine might be useful to prevent overt disease in cattle if administered prior to the exposure of the animal to the disease.
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, modifies the response of cattle to endotoxin (LPS) challenge. Steers (n=16) were divided into the following treatment groups: control(C), ergotamine (ET), endotoxin (LPS), and ET + LPS. ET and ET + LPS groups received a single bolus injection of ET (40 micrograms/kg, bw) whereas C and LPS steers received a single bolus of injection vehicle. Thirty minutes after ET/vehicle administration, a single bolus of LPS (0.2 micrograms/kg, bw) was given. Blood was collected at various timepoints over 48 h. Endotoxin increased rectal temperature (RT) and circulating levels of TNF, cortisol, haptoglobin (Hp), and thromboxane B2 (TBX). The circulating Hp, TBX, and TNF responses were significantly blunted by ET. Ergotamine by itself, increased circulating cortisol and RT, whereas it decreased prolactin levels. Therefore, whereas the administration of LPS to steers resulted in the expected response, the combination of ET + LPS attenuated major effects of LPS alone. Thus acute administration of ET appeared to be anti-inflammatory as it decreased the inflammatory response to LPS, an effect likely driven at least in part by the ET-caused cortisol increases.