AJP - Regulatory, Integrative and Comparative Physiology, Vol 271, Issue 1 185-R190, Copyright © 1996 by American Physiological Society

ARTICLES

Ciliary neurotrophic factor is catabolic and shares with IL-6 the capacity to induce an acute phase response

N. J. Espat, T. Auffenberg, J. J. Rosenberg, M. Rogy, D. Martin, C. H. Fang, P. O. Hasselgren, E. M. Copeland and L. L. Moldawer
Department of Surgery, University of Florida College of Medicine, Gainesville 32610, USA.

Ciliary neurotrophic factor (CNTF), a member of the interleukin-6 (IL-6) superfamily, has recently been shown to induce several inflammatory responses when administered to healthy animals, including induction of fever and a hepatic acute phase protein response. In the present report, 250 micrograms.kg body wt-1.day-1 of recombinant rat CNTF or murine IL-6 were repeatedly administered to healthy mice over a 7-day period in an effort to compare biological responses. In addition to its in vivo capacity to elicit a hepatic acute phase response, administration of CNTF, but not IL-6, produced profound anorexia and lean tissue wasting in mice. In C57B1/6 mice, 7 days of CNTF administration led to a 21% loss in carcass protein content, resulting from carcass protein breakdown rates being increased 218% over freely fed controls (both P < 0.01). Protein synthesis rates in carcass protein were also increased in CNTF-treated mice compared with both freely fed animals and mice pair-fed equivalent quantities of food. In contrast, administration of equivalent quantities of murine IL-6 had no effect on food intake or body weight in mice, although IL-6 produced a similar hepatic acute phase response, as determined by increases in serum amyloid P and seromucoid fraction and increases in total hepatic protein synthesis. However, when CNTF was coincubated with extensor digitorum longus muscles from juvenile rats in vitro, rates of total muscle and myofibrillar protein degradation and muscle protein synthesis were unchanged. We conclude that CNTF can regulate in vivo both skeletal muscle remodeling as well as the distant anorexia and hepatic acute phase protein responses. In the case of skeletal muscle, these actions are both indirect and independent of the associated anorexia. These properties of CNTF are distinct from IL-6, which when administered to the mouse at these doses is neither anorexigenic nor cachexia producing.

This article has been cited by other articles:

				K. A. Baltgalvis, F. G. Berger, M. M. O. Pena, J. M. Davis, S. J. Muga, and J. A. Carson Interleukin-6 and cachexia in ApcMin/+ mice Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2008; 294(2): R393 - R401. [Abstract] [Full Text] [PDF]

				M. J. Tisdale Molecular Pathways Leading to Cancer Cachexia Physiology, October 1, 2005; 20(5): 340 - 348. [Abstract] [Full Text] [PDF]

				S. P. Kalra Circumventing leptin resistance for weight control PNAS, April 10, 2001; 98(8): 4279 - 4281. [Full Text] [PDF]

				H. J. Smith, M. J. Lorite, and M. J. Tisdale Effect of a Cancer Cachectic Factor on Protein Synthesis/Degradation in Murine C2C12 Myoblasts: Modulation by Eicosapentaenoic Acid Cancer Res., November 1, 1999; 59(21): 5507 - 5513. [Abstract] [Full Text] [PDF]

				A. Inui Cancer Anorexia-Cachexia Syndrome: Are Neuropeptides the Key? Cancer Res., September 1, 1999; 59(18): 4493 - 4501. [Abstract] [Full Text] [PDF]

				I. Gloaguen, P. Costa, A. Demartis, D. Lazzaro, A. Di Marco, R. Graziani, G. Paonessa, F. Chen, C. I. Rosenblum, L. H. T. Van der Ploeg, et al. Ciliary neurotrophic factor corrects obesity and diabetes associated with leptin deficiency and resistance PNAS, June 10, 1997; 94(12): 6456 - 6461. [Abstract] [Full Text] [PDF]