Cachectic effect of ciliary neurotrophic factor on innervated skeletal muscle. Martin, David, Evelyn Merkel, Kathy K. Tucker, James L. McManaman, Don Albert, Jane Relton, and Deborah A. Russell. Department of Pharmacology, Synergen Inc., 1885 33rd street, Boulder, CO 80301., Department of Biochemistry (B121), University Colorado Health Science Center, 1200 E. 9th Ave., Denver, CO 80262 and Department of Clinical Operations, Amgen Inc, Boulder, CO 80301
APStracts 3:0181R, 1996.
Recombinant human ciliary neurotrophic factor (rhCNTF) was reported to attenuate skeletal muscle-wasting in rats after unilateral transection of the sciatic nerve (12). Under the experimental conditions reported herein, the absolute masses of the denervated gastrocnemius and soleus muscles were not increased in mature or immature rats of either sex by treatment with rhCNTF. At the highest doses of rhCNTF (1 and 0.1mg/kg), increases in the ratio of the masses of the denervated to the contralateral innervated gastrocnemius and soleus muscles could be attributed entirely to a muscle-wasting effect on the contralateral innervated muscle rather than any muscle-sparing effect on the denervated muscle. The muscle wasting effects of rhCNTF were associated with reductions in body weight gain and reduced food intake. Pair-fed rats lost less body weight and skeletal muscle mass than rhCNTF-injected freely fed rats but experienced significantly greater loss of visceral mass. Male rats displayed greater loss of body weight and skeletal muscle mass than female rats. Recombinant inhibitors of the cachectic cytokines, tumor necrosis factor (TNF) and interleukin-1 (IL-1), did not significantly alter the wasting effects of rhCNTF. These findings demonstrate that in contrast to its well-characterized trophic effects on cells of the nervous system, rhCNTF causes atrophy of skeletal muscle by mechanisms involving both anorexia and cachexia based on the results of pair feeding experiments. 

Received 16 June 1995; accepted in final form 19 April 1996.
APS Manuscript Number R365-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 May 96