Neuronal NF-κB influences thermoregulation and survival in a sepsis model

Gene regulation in sepsis is known to be controlled by the transcription factor NF-κB. However, the function of neuronal NF-κB in sepsis is not well defined. In a mouse model of sepsis induced by i.p. injection of lipopolysaccharides (LPS), we found an activation of NF-κB in the brain as shown by the induction of a transgenic NF-κB reporter. Inhibition of neuronal NF-κB by cell-specific expression of the NF-κB super-repressor IκBα-SR improved LPS-induced hypothermia and survival but had no effect on body weight or on the humoral response to LPS. In contrast, glial inhibition of NF-κB did not influence body temperature and survival. By immunohistochemistry, we detected the active NF-κB subunit RelA in neuronal nuclei of the organum vasculosum of the lamina terminalis. Our data reveal an important role of neuronal NF-κB in thermoregulation and survival. The upcoming group of NF-κB inhibitors may have a place in the treatment of the acute-phase response.