Interleukin-1β in Immune Cells of the Abdominal Vagus Nerve: a Link between the Immune and Nervous Systems?

Abstract

Intraperitoneal administration of the cytokine interleukin-1β (IL-1β) induces brain-mediated sickness symptoms that can be blocked by subdiaphragmatic vagotomy. Intraperitoneal IL-1β also induces expression of the activation marker c-fos in vagal primary afferent neurons, suggesting that IL-1β is a key component of vagally mediated immune-to-brain communication. The cellular sources of IL-1β activating the vagus are unknown, but may reside in either blood or in the vagus nerve itself. We assayed IL-1β protein after intraperitoneal endotoxin [lipopolysaccharide (LPS)] injection in abdominal vagus nerve, using both an ELISA and immunohistochemistry, and in blood plasma using ELISA. IL-1β levels in abdominal vagus nerve increased by 45 min after LPS administration and were robust by 60 min. Plasma IL-1β levels increased by 60 min, whereas little IL-1β was detected in cervical vagus or sciatic nerve. IL-1β-immunoreactivity (IR) was expressed in dendritic cells and macrophages within connective tissues associated with the abdominal vagus by 45 min after intraperitoneal LPS injection. By 60 min, some immune cells located within the nerve and vagal paraganglia also expressed IL-1β-IR. Thus, intraperitoneal LPS induced IL-1β protein within the vagus in a time-frame consistent with signaling of immune activation. These results suggest a novel mechanism by which IL-1β may serve as a molecular link between the immune system and vagus nerve, and thus the CNS.