APPS November 2002 Meeting Abstract 1118


SHORT-TERM INTERLEUKIN-15 TREATMENT DOES NOT ENHANCE FUNCTIONAL REPAIR FOLLOWING SKELETAL MUSCLE INJURY

Anna-Greer Holmes, 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) is a cytokine expressed in skeletal muscle, that can stimulate differentiated myocytes and muscle fibres to accumulate increased amounts of contractile proteins and may play a role in skeletal muscle fibre growth in vivo.1 Exogenous administration of IL-15 has been reported to ameliorate muscle wasting in a rat model of cancer cachexia2, but whether IL-15 has therapeutic potential for enhancing repair of muscle following trauma has not been determined. We tested the hypothesis that exogenous IL-15 administration enhances functional repair of skeletal muscle following injury. Male C57BL/10 ScSn mice (~23 ▒ 1 g, n = 48) were anaesthetised with sodium pentobarbitone and the extensor digitorum longus (EDL) muscle of the right hindlimb was injected with a maximal volume of the myotoxic agent, Marcaine (~ 80-100 ÁL), to cause complete destruction of all muscle fibres. The EDL muscle of the left hindlimb served as the uninjured control. Mice were allocated to a treated group that was administered IL-15 (~0.5 mg/kg/day, s.c.) via osmotic pump for 2, 6, or 10 days, or to an untreated group. Following treatment, the mice were anaesthetised deeply, the EDL muscles excised for assessment of isometric contractile properties in vitro3, and then killed by cardiac excision. In untreated mice, maximum force producing capacity (Po) of injured muscles was 52% and 74% of uninjured control values at 6 and 10 days, respectively. Muscle mass and Po of uninjured muscles were not different between treated and untreated mice. Similarly, treatment did not affect these parameters in the injured muscles at any of the time points studied. We conclude that short-term IL-15 treatment does not enhance the functional properties of regenerating limb muscles following myotoxic injury. The therapeutic potential of IL-15 may be restricted to conditions only where progressive muscle wasting is indicated and hence further evaluation is warranted.

(1) Quinn LS, Haugk KL, Grabstein KH. Endocrinology. 1995;136:3669-3672.

(2) 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.

(3) Lynch GS, Cuffe SA, Plant DR, Gregorevic P. Neuromuscular Disorders. 2001;11:260-268.

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


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