APPS November 2002 Meeting Abstract 1110


INTERLEUKIN-15 ADMINISTRATION IMPROVES DIAPHRAGM MUSCLE FUNCTION IN DYSTROPHIC mdx MICE

Leah J. Harcourt, Paul Gregorevic, Nicole Stupka, David R. Plant, Gordon S. Lynch, Muscle Mechanics Laboratory, Department of Physiology, The University of Melbourne, Victoria, 3010, Australia.

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 (sPo, force per cross-sectional area) of the diaphragm of control mice (untreated (n = 7): 206 6 vs. treated (n = 4): 204 9 kN/m2). In contrast, the sPo of diaphragm muscle strips from IL-15 treated mdx mice was greater than in untreated mdx mice (untreated (n = 7): 110 9 vs. treated (n = 6): 141 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.

(1) Carbo N, Lopez-Soriano J, Costelli P, Busquets S, Alvarez B, Baccino FM, Quinn LS, Lopez-Soriano FJ, Argiles JM. British Journal of Cancer. 2000;83:526-531.

(2) Lynch GS, Rafael JA, Hinkle RT, Cole NM, Chamberlain JS, Faulkner JA. American Journal of Physiology. 1997;272:C2063-C2068.

(3) Gregorevic P, Plant DR, Leeding KS, Bach LA, Lynch GS. American Journal of Pathology. 2002;(in press).

IL-15 was kindly provided by Immunex Corporation (Seattle, Washington). This work was supported by the Muscular Dystrophy Association (USA).


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