The protective effects of chronic intermittent hypobaric hypoxia pretreatment against collagen-induced arthritis in rats

Objective: To explore the immunological mechanisms underlying the effect of chronic intermittent hypobaric hypoxia (CIHH) pretreatment on collagen-induced arthritis (CIA) in rat. Methods: Fifty-four adult male Sprague-Dawley rats were used in the experiment. Arthritis in CIA rats (n=18) was induced by injection of collagen. The CIHH+CIA rats (n=18) were treated with CIHH (simulated 3000 m altitude, 5 hours per day for 28 days, PO2=108.8 mmHg) before CIA. The control rats (n=18) were not given any treatment. Results: (1) Incidence rate of CIA in CIHH+CIA rats was significantly lower than that in CIA rats (P<0.05). (2) The paw thickness and arthritis index (AI) value in CIHH+CIA rats were lower than those in CIA rats (P<0.05). (3) The hyperplasia with inflammatory infiltration in synovial tissue of joints in CIHH+CIA rats was much alleviative compared with CIA rats. (4) TNF-alpha, IFN-gamma, IL-4 and IL-17 in synovial tissue of joint and serum in CIHH+CIA rats were decreased compared with CIA rats (P<0.05). (5) The number of CD4-positive T-lymphocytes and the ratio of CD4/CD8 T-lymphocytes in peripheral blood in CIHH+CIA rats were lower than those in CIA rats (P<0.05). (6) The protein expression of HIF-1 alpha and NF-kappa B in synovial tissue of joint in CIHH+CIA rats was decreased compared with CIA rats (P<0.05). Conclusion: CIHH pretreatment has a protective effect against collagen-induced arthritis in rat through down-regulation of HIF-1 alpha and NF-kappa B, inhibition of inflammatory cytokines TNF-alpha and IL-17, and balance in CD4/CD8 and Th1/Th2 T lymphocytes.