Relationship of exercise-induced core temperature elevation to fever: Involvement of tumor necrosis factor, prostaglandin, and corticotropin releasing factor.

Abstract

The experiments described in this dissertation were designed to test the hypotheses that tumor necrosis factor (TNF), prostaglandin and corticotropin releasing factor (CRF) are involved in the exercise-induced elevation in core temperature. To test these hypotheses, female Sprague Dawley rats were given access to running wheels. We found the body temperature of the exercising animals to be elevated above sedentary controls, even during periods of inactivity (daytime) suggesting that voluntary exercise in the female rat causes an elevation of the temperature set-point. To determine whether TNF (Chapter 3) was responsible for part of the exercise-induced rise in daytime temperature, antiserum to TNF, injected ip at a dose that altered tumor-induced changes in body temperature and LPS-induced fever, or control serum were injected into female rats with access to running wheels 3 hours after the lights-on period. Neither ip injection of antiserum against TNF or control serum had any effect on daytime temperature elevation seen in exercising female rats. To assess whether this exercise-induced elevation in daytime temperature was mediated by a cyclooxygenase pathway, we injected animals with a dose of sodium salicylate (Chapter 4), which we showed to block fevers caused by an ip injection of lipopolysaccharide (LPS). Injection of sodium salicylate did not result in any suppression of this daytime elevation in body temperature of exercised rats. To assess whether CRF was responsible for part of the exercise-induced rise in daytime temperature, a monoclonal antibody to CRF was administered (Chapter 5). We injected intracerebroventricularly (icv) a similar dose of antibody that had been shown to significantly attenuate the fever response to IL-1$\beta$. Injection of anti-CRF or vehicle had no effect on the body temperature of sedentary animals. However, when anti-CRF was given to exercising animals, the exercising animals showed significantly attenuated body temperatures one day post-injection. Injection of vehicle had no effect on body temperature of exercising animals. Based on these data, we conclude that the exercise-induced elevation in body temperature could be due, in part, to an increased secretion or action of CRF.