Dose-related effects of recombinant human interleukin-10 on hypoxia-induced skeletal muscle injury in immature rats.
BACKGROUND: The role of cytokines in the pathogenesis of skeletal muscle injury in patients with hypoxia and inflammation remains unclear. The aim of the present study was to determine the dose-related effects of recombinant human interleukin-10 (rhIL-10) on hypoxia-induced skeletal muscle injury in immature rats. METHODS: The study was performed on 1-day-old Sprague-Dawley rat pups that were randomized to one of five groups: nonhypoxic controls (group 1; n=8); rats subjected to hypoxia-reoxygenation (H/O) and returned to their mothers (group 2; n=11); rats subjected to H/O, returned to their mothers, and treated with rhIL-10 (10 microg/kg per day s.c.) for 3 days (group 3; n=10); rats subjected to H/O, returned to their mothers, and treated with rhIL-10 (25 microg/kg per day s.c.) for 3 days (group 4; n=10); or rats subjected to H/O, returned to their mothers, and treated with rhIL-10 (75 microg/kg per day s.c.) for 3 days (group 5; n=10). All animals were killed on day 4, and skeletal muscle specimens were obtained to determine the tissue levels of malondialdehyde (MDA) and superoxide dismutase (SOD) and to check for any histological changes. RESULTS: The polymorphonuclear leukocyte count, amount of interstitial edema, microvessel size, and area of myocyte necrosis was greater in groups 2, 3, 4, and 5 than in group 1, although the findings were significantly less prominent in groups 4 and 5 than in groups 2 and 3. MDA levels significantly increased in groups 2 and 3 compared to those in groups 1, 4, and 5. SOD values decreased significantly in groups 2 and 3 compared to those in groups 1, 4, and 5. CONCLUSIONS: Administration of rhIL-10 reduced skeletal muscle injury produced by hypoxia in immature rats. Intermediate and high doses of rhIL-10 were associated with a significant reduction of skeletal muscle damage, whereas a low dose was not.