IL-1β inhibits IK and increases [Ca2+]i in the carotid body glomus cells and increases carotid sinus nerve firings in the rat

Increasing evidence indicates that there exists a reciprocal communication between the immune system and the brain. Interleukin 1 beta (IL-1 beta), a proinflammatory cytokine produced during immune challenge, is believed to be one of the mediators of immune-to-brain communication, but how it gets into the brain is unknown because of its large molecular weight and difficulty in crossing the blood-brain barrier. Our previous work has demonstrated that IL-1 receptor type I is strongly expressed in the glomus cells of rat carotid body (CB), a well characterized polymodal chemoreceptive organ which serves not only for the detection of hypoxia, hypercapnia and acidity, but also for low temperature and blood glucose. The present study was designed to test whether IL-1 beta could stimulate the CB glomus cells and alter the discharge properties in the carotid sinus nerve, the afferent nerve innervating the organ. The results from whole-cell patch-clamp recordings and calcium imaging showed that extracellular application of IL-1 beta significantly decreased the outward potassium current and triggered a transient rise in [Ca2+](i) in the cultured glomus cells of rat CB. Furthermore, by using extracellular recordings and pharmacological intervention, it was found that IL-1 beta stimulation of the CB in the anaesthetized rat in vivo significantly increased the discharge rate in the carotid sinus nerve, most probably mediated by ATP release. This experiment provides evidence that the CB responds to cytokine stimulation and proposes the possibility that the CB might play a role in immune-to-brain communication.