Murine Pro-Inflammatory Responses to Acute and Sustained Intermittent Hypoxia: Implications for Obstructive Sleep Apnea Research

Objectives: Obstructive sleep apnea (OSA) is characterized by chronic systemic inflammation; however, the mechanisms underlying these pathologic consequences are incompletely understood. Our objective was to determine the effects of short-versus long-term exposure to intermittent hypoxia (IH) on pro-inflammatory mediators within vulnerable organs impacted by OSA. Study Design: Experimental animal study. Methods: A total of 8-10 week old C57BL/6J mice were exposed to normoxic or IH conditions for 7 days (short-term) or 6 weeks (long-term) under 12 h light, 12 h dark cycles. After exposure, multiple tissues were collected over a 24 h period. These tissues were processed and evaluated for gene expression and protein levels of pro-inflammatory mediators from peripheral tissues. Results: We observed a global decrease in immune response pathways in the heart, lung, and liver compared with other peripheral organs after short-term exposure to IH. Although there were tissue-specific alterations in the gene expression of pro-inflammatory mediators, with down-regulation in the lung and up-regulation in the heart, we also observed reduced protein levels of pro-inflammatory mediators in the serum, lung, and heart following short-term exposure to IH. Long-term exposure to IH resulted in an overall increase in the levels of inflammatory mediators in the serum, lung, and heart. Conclusions: We demonstrated novel, longitudinal changes in the inflammatory cascade in a mouse model of OSA. The duration of exposure to IH led to significant variability of inflammatory responses within blood and cardiopulmonary tissues. Our findings further elucidate how inflammatory responses change over the course of the disease in vulnerable organs.