DIURNAL, AGE, AND IMMUNE REGULATION OF INTERLEUKIN-1β AND INTERLEUKIN-1 TYPE 1 RECEPTOR IN THE MOUSE SUPRACHIASMATIC NUCLEUS

Circadian clocks serve to impose a near-24-h temporal architecture on an organism's physiology, metabolism, and behavior. In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus functions as the master circadian pacemaker. There is growing evidence that immunomodulators, such as cytokines, may impinge on circadian timekeeping. We examined whether there is endogenous expression of the proinflammatory cytokine interleukin-1 beta (IL-1 beta) and its signaling receptor IL-1R1 in the SCN of young and older mice across the diurnal cycle. We found expression of both IL-1 beta and IL-1R1 in the young SCN, although only IL-1R1 displayed temporal regulation. In the older SCN, levels of IL-1 beta were expressed at lower levels than in the young SCN, and IL-1R1 did not vary across the 24 h. We also report age-related day-night variation of IL-1 beta and IL-1R1 in the paraventricular nucleus (PVN) of the hypothalamus. Further, we examined the effect of peripheral immune challenge on IL-1 beta and IL-1R1 in the SCN. We found that IL-1 beta immunoreactivity was not altered 6 or 24 h after a septic dose of lipopolysaccharide (LPS; 5 mg/kg), whereas IL-1R1 was significantly up-regulated in the SCN both 6 and 24 h after LPS. We also demonstrate cellular activation in the SCN 24 h following LPS treatment, as evidenced by increased c-Fos and p65-NF-kappa B (nuclear factor kappa B) expression. Our results indicate that IL-1 beta and its associated signaling system may play a role in mediating the response of the circadian timing system to immune challenge as well as potentially contributing to the basal functioning of the SCN clock. (Author correspondence: andrew.coogan@nuim.ie)