Chronic hypoxia (CH)‐induced inflammation and the effect of interleukin‐6 (IL‐6) gene deletion on chemoreceptor adaptation in mouse carotid body (CB)

Abstract

Exposure to CH elicits a marked increase in chemosensory excitability in the mammalian CB. In chronic inflammatory pain unique hyperexcitable phenotypes emerge in primary afferent neurons as a consequence of invasive activated immune cells and their secretory cytokine products. The present study examines the effect of CH on the expression of inflammatory cytokines in mouse CB, and the effect of IL-6 gene knockout (KO) on CH-induced chemoreceptor hyperexcitability. Real-time quantitative PCR showed that 1, 3 or 7 days of hypobaric hypoxia (BP = 380 Torr) elicited significant increases (4–12 fold) in the expression of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). In addition, the chemokine, monocyte chemoattractant protein-1 (MCP-1), was increased 6-, 31- and 41-fold, on days 1, 3, and 7 of CH, respectively. In vitro recordings of carotid sinus nerve (CSN) activity showed that following 10–12 days of CH, responses evoked by an acute hypoxic challenge were increased by approximately 30% in normal mice. Responses to acute hypoxia were similar to normal in IL-6 KO preparations, but following CH they were not elevated. The data are in agreement with our previous findings that CH elicits an inflammatory condition in rat CB, and they further suggest that increased cytokine production is critical for adaptation and the development of hypersensitivity. USPHS Grants NS 12636 and NS 07938.