Studies in this proposal focus on the mechanism by which the acute-phase proteins a1-antitrypsin (AAT) and a2-macroglobulin (AMG) act as positive modulators of fever. Because these proteins are protease inhibitors, the investigators hypothesize that they act by increasing the concentrations of pyrogenic cytokines in the circulatory system and the hypothalamus. The proposed studies are to test two potential models.
The specific aims are to: 1. Test the hypothesis that AAT acts as an endogenous pyrogen during LPS-induced fever; 2. Test the hypothesis that AMG acts as an endogenous pyrogen during LPS-induced fever; 3. Test the hypothesis that circulating AAT and AMG modulate fever via the regulation of cytokine clearance.
Gourine, Alexander V; Gourine, Valery N; Tesfaigzi, Yohannes et al. (2002) Role of alpha(2)-macroglobulin in fever and cytokine responses induced by lipopolysaccharide in mice. Am J Physiol Regul Integr Comp Physiol 283:R218-26 |