Time‐course of cytokine expression and immune cell invasion induced in rat carotid body by chronic hypoxia

Recent studies in our laboratory suggest that chemoreceptor adaptation in carotid body is mediated by immune cell invasion and cytokine expression. In chronic neuropathic pain immune cell recruitment is triggered by production of inflammatory cytokines in Schwann cells distal to a nerve lesion (Shamash, et al., J. Neurosci. 22:3052,2002), leading to primary sensory neuron hyperexcitability and hyperalgesia. The present study uses quantitative RT‐PCR (qPCR) to compare the time‐courses of inflammatory cytokine production versus immune cell invasion in carotid bodies exposed to hypobaric hypoxia (380 Torr). IL‐6 expression increased 2‐fold after 24h, and 8‐fold and 12‐fold, respectively, following 3 and 7 days of CH. IL‐1β and tumor necrosis factor‐α were not changed following 24h, but were significantly increased at 3 and 7 days of low O 2 . Markers for immune cell invasion, including CD14 and the gp91 phox , were not changed following 24h of hypoxia. However, expression of these genes was increased 2–3‐fold in carotid body at 3 and 7 days of CH. Likewise, the expression of the chemokine, monocyte chemoattractant protein‐1 (MCP‐1), increased at 3 (2‐fold) and 7 (4.5‐fold) days, but not following 1 day of hypoxia. Present data are consistent with the hypothesis that prolonged hypoxia‐induced depolarization of type I cells elicits IL‐6 production which activates a cytokine network resulting in MCP‐1 expression, recruitment of circulating leukocytes, and enhanced cytokine activity. Supported by USPHS grants NS 12636 and NS 17928.