Effects of Acute Exposure to Hypobaric Hypoxia on Mucosal Barrier Injury and the Gastrointestinal Immune Axis in Rats.

Khanna, Kunjan, K.P. Mishra, Sudipta Chanda, Malleswara Rao Eslavath, Lilly Ganju, Bhuvnesh Kumar, and Shashi Bala Singh. Effects of acute exposure to hypobaric hypoxia on mucosal barrier injury and the gastrointestinal immune axis in rats. High Alt Med Biol 00:000-000, 2018.-High altitude-induced gastrointestinal (GI) problems are potentially life-threatening. GI tract bleeding and inflammation are the major problems induced by hypobaric hypoxia (HH). In this study, effects of acute exposure to HH up to 14 days at 7620 m on GI immune function have been studied. To fulfill these objectives, Sprague-Dawley (SD) rats were divided into five groups namely Control and HH exposed (1, 3, 7, and 14 days). All groups except control were exposed to 7620 m of HH in an animal decompression chamber for the respective time intervals. Different degrees of intestinal mucosal damage in terms of increased mucosal permeability and disruption of intestinal villi were observed for different time intervals. HH exposure also upregulated secretory immunoglobulin A (sIgA) and proinflammatory cytokines in GI lavage along with proinflammatory markers such as toll-like receptor 4 (TLR4) and inducible nitric oxide synthase (iNOS). HH exposure of rats for 7 days significantly increased interleukin-17 (IL-17) and natural killer (NK) cell and dendritic cell populations compared with unexposed control rats. However, the number of naive T cells was significantly decreased in Peyer's patches. Our results connect HH to GI immune axis and highlight Th17 cells and proinflammatory molecules as potential therapeutic targets to counteract HH-induced GI dysfunction.