128. Selective contributions of neuronal and astroglial interleukin-1 receptor 1 to behavioral immune responses

Abstract

Immune challenges alter central nervous system (CNS)-mediated processes; however, the mechanisms by which the CNS regulates behavior and physiology during immune responses are not fully understood. We hypothesize that neuronal-glial interactions, mediated by cytokines, contribute to altered behavior during immune challenges. To this end, we engineered two transgenic mouse lines that express interleukin-1 receptor 1 (IL1R1) only in the CNS and selectively on neurons or astrocytes. These mice express murine IL1R1 cDNA under transcriptional control of the neuron-specific enolase (NSE) or the human glial fibrillary acidic protein (gfa2) promoters. The transgenes were bred onto a genetic background lacking endogenous IL1R1 expression centrally and peripherally. Animals with selective neuronal IL1R1 expression are referred to as NSE-IL1R1, and strains expressing IL1R1 on astrocytes are called gfa2-IL1R1. Transgenic mice instrumented with cranial electroencephalographic electrodes and a thermistor were injected intracerebroventricularly with 50 ng IL-1 beta or intraperitoneally with lipopolysaccharide (LPS; 0.40 mg/kg). Preliminary data from ongoing studies suggest that IL-1 beta induces rapid eye movement sleep (REMS) suppression in NSE-IL1R1 mice that is of greater magnitude than REMS responses of gfa2-IL1R1 mice. Similarly, early results indicate systemic challenge with LPS induces fever and suppresses REMS to a greater extent in NSE-IL1R1 mice than in gfa2-IL1R1 mice. These encouraging results suggest a potential role for neurons as primary effectors of cytokine activity in mediating behavioral responses to immune challenge.