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 pro-inflammatory cytokines, activated macrophages and other leukocytes to secrete hydroxyl radical (OH), nitric oxide metabolites (NO(x)(-)), superoxide (O(2)) and other reactive oxygen/nitrogen species. Furthermore, inflammation response-associated hypoxia stimulated glutamate release, which caused excitotoxicity of cells by increasing extracellular Ca(2+). Cytokines and glutamate in turn also triggered the release of large amounts of NO(x)(-), OH, O(2), 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, NO(x)(-), 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), NO(x)(-) and OH generated in the hypothalamus during pyrogenic fever was attempted hereby. To find the link among the signaling with the glutamate, NO(x)(-) and OH/prostaglandin E(2) in the hypothalamus during pyrogenic fever will be challenging and could now clinically suppress pyrogenic fever.