54. Nuclear factor interleukin 6 deficient mice show reduced locomotor activity and dose dependant alterations in fever and recruitment of neutrophil granulocytes to the brain during LPS-induced systemic inflammation

A role for the inflammatory transcription factor nuclear factor interleukin-6 (NF-IL6) was previously proposed for brain inflammation, fever and recruitment of neutrophil granulocytes (NG) to the brain during systemic inflammation. Here, lipopolysaccharide (LPS, 2500 or 50 μg/kg i.p.) was used to induce systemic inflammation in NF-IL6 deficient or wildtype mice. The sickness response was monitored by a telemetric system, animals were sacrificed 8 or 24 h after stimulation, brains and blood samples collected and analysed using immunohistochemistry, RT-PCR and a cytokine-bioassay to detect markers of brain inflammation, brain-immigrated NGs as well as plasma IL-6 levels. Knockout mice showed reduced basal temperature during the night and reduced basal nocturnal activity. LPS-induced anorexia and adipsia only occurred after injection with the high dose of LPS in NF-IL6KO animals, while fever was prolonged after low- and abolished for 8 h after high-dose LPS-stimulation. This response was accompanied by increased IL-6-plasma levels at 8 h that decreased to baseline 24 h after LPS-injection in both genotypes. NGs were recruited to different brain structures including the subfornical organ (SFO) and the paraventricular nucleus of the hypothalamus 24 h after high dose stimulation; in NF-IL6KO mice immigration of NGs to SFO was decreased, but increased to fimbria of the hippocampus. Overall, we showed that NF-IL6 is essential for regulation of activity and fever (dose-dependent) and modulates recruitment of NG to the brain (pathways are under investigation).