Oxidative stress and pyrogenic fever pathogenesis

The causative/regulatory connections between changes in tissue redox state and fever induction were investigated herein. Wherefore, LPS, the primary element of bacterial cell wall, in addition to inducing proinflammatory cytokines, activated macrophages and other leukocytes to secrete hydroxyl radical (OH), nitric oxide metabolites (NOx-), superoxide (O-2 center dot) and other reactive oxygen/nitrogen species. Furthermore, inflammation response-associated hypoxia stimulated glutamate release, which caused excitotoxicity of cells by increasing extracellular Ca2+. Cytokines and glutamate in turn also triggered the release of large amounts of NOx-, OH, O-2 center dot, and other radicals. Those reactive nitrogen species in turn caused cellular injury via the peroxidation of membrane lipids and oxidative damage of proteins and DNA. Glutamate, NOx-, OH and antioxidants participated in the pathogenesis and regulation of LPS- or cytokines-induced fever. In particular, to highlight the role of glutamate, prostaglandin E-2, NOx- and OH generated in the hypothalamus during pyrogenic fever was attempted hereby. To find the link among the signaling with the glutamate, NOx- and OH center dot/prostaglandin E-2 in the hypothalamus during pyrogenic fever will be challenging and could now clinically suppress pyrogenic fever. (C) 2011 Elsevier By. All rights reserved.