Oxidative stress and pyrogenic fever pathogenesis

Abstract

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.