METABOLIC AND ENDOCRINE EFFECTS OF ENDOTOXIN: SOURCES OF VARIABILITY IN THE HOST RESPONSE

Authors: Elsasser, Theodore; BLUM, J. - UNIV.BERNE, SWITZERLAND; Kahl, Stanislaw; SARTIN, J. - AUBURN UNIVERSITY

Submitted to: Meeting Abstract
Publication Type: Proceedings
Publication Acceptance Date: 3/5/2005
Publication Date: N/A
Citation: N/A

Interpretive Summary: Many diseases of food animals are actually brought on by toxins released from the cell membranes of the bacteria infecting the animals. Endotoxin is one such bacterial toxin and its introduction into an animal triggers many events that are harmful to the animal. The severity of the response to endotoxin by a subject is dose-dependant. Some of the more severe effects of endotoxin on animals is the stark changes in metabolism that occur. There are many reasons for these metabolic changes and these include severe blood flow changes to and from important organs, changes in the production of and response to the animals own metabolic hormones, and alterations in what the animal's body perceives as important for survival to the insult. There are many influences besides dose of exposure to the endotoxin that determine the severity of the animal's response. These include the quantity and quality of the feed that the animal receives, the sex of the animal, the stage of the estrus cycle, season, ambient temperature, breed and several genetic factors that determine how large the immune response to the toxin will be. It is important for veterinarians to know the signs of endotoxemis and these include lethargy, poor food intake, fever, and weight loss; in severe endotoxemia animals will shiver, breathe hard and be very slow to recover. The end result of the animal's response to endotoxin will be poor growth for a period of time in young animals, and a significant decline in milk production in dairy animals. In addition, prolonged endotoxemia in the pregnant animals can result in the loss of the calf. Treatment of the animal can include measures to stop the release of the immune hormones that mediate the response as well as measures to stabilize aspects of physiology that become compromised. Anti-inflammation drugs like Banamine are beneficial in recovery as is the intravenous administration of salts and glucose.

Technical Abstract: Introduction of endotoxin (LPS) into the internal environment initiates a dose-dependent activation of cascading responses directed through a well timed elaboration of cytokine fluxes, prostaglandins, glucocorticoids, and the activation of discrete aspects of the nitric oxide generating pathway. In the younger, growing animal, initial responses to LPS involve a redirection of metabolism wherein nutrients are channeled away from anabolic activities to support immune and homeostatic mechanisms, especially where intake is compromised. In experimental challenges with exogenous LPS, in a graded manner we can observe changes in metabolic hormones consistent with the patterns of metabolite changes indicative of the progression into and recovery from glycolysis, lipolysis, insulin resistance, peripheral protein degradation and induction of hepatic synthesis of acute phase response proteins. Many of the effects of LPS on metabolic and reproductive function can be linked to cytokine modulation of hypothalamic and pituitary hormone secretion and consequential changes in the sensitivity and responsiveness of peripheral tissues to hormones of the somatotropic axis (growth hormone and insulin-like growth factor-1), reproductive steroids (estrogen and progesterone) and E- and F-series prostaglandins. Prevailing physiological state, i.e., reproductive status or plane of nutrition, at the time of LPS encounter largely accounts for much of the animal-to-animal variability observed in the response to a given dose of LPS and, in particular, how the propensity for the development of the tolerance response to prolonged or repeated LPS exposure is maintained or lost. Cytokine and metabolic responses to LPS are augmented where the administration of LPS occurs in conjunction with the presence of underlying clinical and subclinical infection. Because many of the deleterious effects of LPS on metabolism can be tracked back to an aberrant production of free radicals and reactive nitrogen species, beneficial effects of antioxidant treatment, for example with vitamin E administration, prior to the LPS exposure are observed. Finally, the capability for tissues to respond directly to LPS is suggested by the localization of CD14 receptors on many metabolically important tissues including adipose and pituitary.