APPS November 2002 Meeting Abstract 1110

Interleukin-15 (IL-15), a recently discovered growth factor that is highly expressed in skeletal muscle, has recently been shown to ameliorate muscle wasting in a rat model of cancer cachexia.¹ Severe and progressive wasting and weakness also occurs in the muscles of boys with Duchenne muscular dystrophy (DMD). The mdx mouse has a similar genetic defect to that in DMD, but only the diaphragm muscle of these mice exhibits a similar pathology.². The purpose was to investigate the role of exogenous IL-15 administration for ameliorating the dystrophic symptoms and loss of function in the diaphragm muscles of mdx mice. Nine week old mdx and C57BL/10 ScSn control mice were administered IL-15 (~0.5 mg/kg/day, s.c.) via a mini osmotic pump for 4 weeks. At the conclusion of treatment, mice were anaesthetised with sodium pentobarbitone and the diaphragm excised and isometric contractile properties of isolated muscle strips determined in vitro using methods described previously.^2,3 Preliminary results indicate that 4 weeks' treatment with IL-15 does not alter specific force (sP_o, force per cross-sectional area) of the diaphragm of control mice (untreated (n = 7): 206 ą 6 vs. treated (n = 4): 204 ą 9 kN/m²). In contrast, the sP_o of diaphragm muscle strips from IL-15 treated mdx mice was greater than in untreated mdx mice (untreated (n = 7): 110 ą 9 vs. treated (n = 6): 141 ą 2 kN/m², P < 0.05). These preliminary data demonstrate that IL-15 administration has the potential to improve functional properties of respiratory muscles in mdx mice. Since respiratory function is a mortality predictor in DMD patients, further evaluation of the therapeutic potential of IL-15 is recommended.