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.
Ozturk
Kahraman
K
Department of Orthopaedics and Traumatology, Baltalimani Metin Sabanci Training and Research Hospital for Bone Diseases, Istanbul University Faculty of Medicine, Turkey.
Demir
Bilal
B
Oke
Ramadan
R
Durmaz
Hayati
H
D000818:Animals; D000831:Animals, Newborn; D015687:Cell Hypoxia; D004305:Dose-Response Relationship, Drug; D006651:Histocytochemistry; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D008315:Malondialdehyde / Q000032:analysis; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000293:injuries*; D018384:Oxidative Stress / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000188:drug therapy*; D013482:Superoxide Dismutase / Q000032:analysis
C508609:IL10 protein, human; D011994:Recombinant Proteins; D016753:Interleukin-10; D008315:Malondialdehyde; D013482:Superoxide Dismutase