Effects of intermittent hypoxia training on cytokine responses to exercise

The primary rationale for clinical use of intermittent hypoxia (IH) is the potential cross-protective value of adaptation to one stress, which then provides resistance to another stress. Acclimatization to IH causes a progressive increase in pulmonary ventilation, adaptation of the circulatory system to enhance delivery of oxygen to tissues, and changes at the tissue level that optimize utilization of oxygen, thereby improving aerobic capacity and resistance to acute hypoxic stress. However, the long-term consequences of IH may be detrimental, including pulmonary and systemic hypertension, neuropathological and neurocognitive deficits, and enhanced susceptibility to oxidative injury. The IH associated with obstructive sleep apneas syndrome (OSAS) selectively activates the pro-inflammatory transcription factor, nuclear factor-B (NF B), whereas downstream products of NF B activation, such as tumor necrosis factor-, have been reported to be elevated in OSAS patients. The adverse events evoked by the pathological IH may result from disturbed redox homeostasis in the organism. Systemic administration of an antioxidant can suppress lipid peroxidation and protect against the adverse effects in a pathological IH setting. Another IH pattern comprises long daily sustained hypoxic exposure (hours) over periods ranging from weeks to months. Recent studies indicated that the IH regimens with bouts of sustained hypoxic exposure impact inflammationrelated cytokine releases caused by strenuous exercise through modulating redox status in circulation, with reactions determined by the intervening IH condition. Either severe IH or moderate IH (i.e., 12% O2 or 15% O2 for 1 hour/day, 5 days/week for 8 weeks) can simultaneously hinder lipid peroxidation and pro-inflammatory cytokine interleukin (IL)-1 production generated by vigorous exercise. Furthermore, chronic severe IH is associated with increased anti-inflammatory cytokine IL-6 and IL-10 contents in circulation. By elucidating the relationships between various IH patterns and cytokinemediated physiological and pathophysiological effects, this study attempts to provide a strategy for developing suitable IH regimens that improve aerobic capacity and simultaneously minimize risk of inflammation-related disorders.