• Eric Jüttler, Ioana Inta, Verena Eigler, Oliver Herrmann, Ira Maegele, Christiane Maser-Gluth, and Markus Schwaninger.
• Department of Neurology, University of Heidelberg, Im Neuenheimer Feld 400, D-69120 Heidelberg, Germany.
• J. Neuroimmunol. 2007 Sep 1; 189 (1-2): 41-9.

AbstractGene regulation in sepsis is known to be controlled by the transcription factor NF-kappaB. However, the function of neuronal NF-kappaB 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-kappaB in the brain as shown by the induction of a transgenic NF-kappaB reporter. Inhibition of neuronal NF-kappaB by cell-specific expression of the NF-kappaB super-repressor IkappaBalpha-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-kappaB did not influence body temperature and survival. By immunohistochemistry, we detected the active NF-kappaB subunit RelA in neuronal nuclei of the organum vasculosum of the lamina terminalis. Our data reveal an important role of neuronal NF-kappaB in thermoregulation and survival. The upcoming group of NF-kappaB inhibitors may have a place in the treatment of the acute-phase response.

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