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EDITORIAL FOCUS

Adaptation to chronic hypoxia involves immune cell invasion and increased expression of inflammatory cytokines in rat carotid body

Department of Physiology, University of Utah School of Medicine, Salt Lake City, Utah

Submitted 16 July 2008 ; accepted in final form 29 October 2008

Exposure to chronic hypoxia (CH; 3–28 days at 380 Torr) induces adaptation in mammalian carotid body such that following CH an acute hypoxic challenge elicits an abnormally large increase in carotid sinus nerve impulse activity. The current study examines the hypothesis that CH initiates an immune response in the carotid body and that chemoreceptor hyperexcitability is dependent on the expression and action of inflammatory cytokines. CH resulted in a robust invasion of ED1⁺ macrophages, which peaked on day 3 of exposure. Gene expression of proinflammatory cytokines, IL-1β, TNF, and the chemokine, monocyte chemoattractant protein-1, was increased >2-fold after 1 day of hypoxia followed by a >2-fold increase in IL-6 on day 3. After 28 days of CH, IL-6 remained elevated >5-fold, whereas expression of other cytokines recovered to normal levels. Cytokine expression was not restricted to immune cells. Studies of cultured type I cells harvested following 1 day of in vivo hypoxia showed elevated transcript levels of inflammatory cytokines. In situ hybridization studies confirmed expression of IL-6 in type I cells and also showed that CH induces IL-6 expression in supporting type II cells. Concurrent treatment of CH rats with anti-inflammatory drugs (ibuprofen or dexamethasone) blocked immune cell invasion and severely reduced CH-induced cytokine expression in carotid body. Drug treatment also blocked the development of chemoreceptor hypersensitivity in CH animals. Our findings indicate that chemoreceptor adaptation involves novel neuroimmune mechanisms, which may alter the functional phenotypes of type I cells and chemoafferent neurons.

dexamethasone; interleukin-1β; interleukin-6; tumor necrosis factor-

This article has been cited by other articles:

				F. L. Powell Adaptation to chronic hypoxia involves immune cell invasion and increased expression of inflammatory cytokines in rat carotid body Am J Physiol Lung Cell Mol Physiol, February 1, 2009; 296(2): L156 - L157. [Full Text] [PDF]