INTERLEUKIN-15 - A NOVEL ANABOLIC CYTOKINE FOR SKELETAL-MUSCLE

Interleukin-15 (IL-15) is a recently discovered growth factor which is highly expressed in skeletal muscle. In order to determine a function al role for IL-15 in skeletal myogenesis, the effects of IL-15 on myob last proliferation and muscle-specific myosin heavy chain (MHC) expres sion were analyzed using the mouse C2 skeletal myogenic cell line and primary fetal bovine skeletal myogenic cultures. IL-15 had no effect o n [H-3]thymidine incorporation, nor on the rate of myoblast differenti ation, assessed by anti-MHC immunocytochemical staining, in either typ e of culture. However, Western blot analyses revealed that IL-15 used at concentrations of 10 or 100 ng/ml increased MHC accumulation five-f old in C2 myoblast cultures and 2.5-fold in primary bovine myogenic cu ltures. Moreover, C2 myotubes formed in the presence of IL-15 appeared larger than controls. These findings indicate IL-15 can stimulate dif ferentiated myocytes and muscle fibers to accumulate increased amounts of contractile proteins. Well-fused primary bovine myogenic cultures treated with the mitotic inhibitor aphidicolin, then administered IL-1 5 and/or the anabolic growth factor insulin-like growth factor-I (IGF- I), were analyzed for MHC accumulation using Western blots. IL-15 used at 10 ng/ml doubled MHC accumulation and was as effective as IGF-I us ed at 10 or 100 ng/ml. IL-15 and IGF-I used together increased MHC acc umulation close to five-fold, indicating these two factors can act add itively on muscle fibers. These findings indicate IL-15 affects parame ters associated with skeletal muscle fiber hypertrophy, and suggest th at IL-15 may be a novel anabolic agent to increase skeletal muscle mas s.