AJP - Endocrinology and Metabolism, Vol 265, Issue 4 E660-E666, Copyright © 1993 by American Physiological Society

ARTICLES

Pentoxifylline decreases body weight loss and muscle protein wasting characteristics of sepsis

D. Breuille, M. C. Farge, F. Rose, M. Arnal, D. Attaix and C. Obled
Laboratoire d'Etude du Metabolisme Azote, Institut National de la Recherche Agronomique, Theix, Ceyrat, France.

Sepsis induces metabolic disorders that include loss of body weight, muscle wasting, and acute-phase protein synthesis in liver. Cytokines are generally recognized as active mediators of these disorders, and the implication of tumor necrosis factor (TNF) has been frequently discussed in the recent past. However, the identity of the active agent in alterations of protein metabolism is still controversial. To improve our understanding of the role of cytokines in mediating muscle wasting observed in sepsis, we investigated muscle and liver protein metabolism in the following three groups of rats: infected control rats (INF-C); infected rats pretreated with pentoxifylline (PTX-INF), which is a potent inhibitor of TNF secretion; and pair-fed rats for the PTX-INF group pretreated with pentoxifylline. Pentoxifylline nearly completely suppressed TNF secretion but did not influence the transient fall in rectal temperature, the decreased hematocrit, and the increased liver protein mass and synthesis observed in INF-C rats. Pentoxifylline decreased the anorexia, the loss of body weight and muscle protein observed in INF-C animals, and partially prevented the decrease in muscle protein synthesis induced by infection. The overall data indicate that pentoxifylline is an effective agent in mitigating the characteristic muscle protein wasting induced by sepsis and confirm the limited role of TNF in the mediation of the acute-phase protein synthesis. Our results suggest a probable implication of TNF in the regulation of protein balance in muscle but do not allow discarding possible implication of other mediators that would be inhibited by pentoxifylline.

This article has been cited by other articles:

				A. M. Baviera, N. M. Zanon, L. C. Carvalho Navegantes, R. H. Migliorini, and I. d. C. Kettelhut Pentoxifylline inhibits Ca2+-dependent and ATP proteasome-dependent proteolysis in skeletal muscle from acutely diabetic rats Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E702 - E708. [Abstract] [Full Text] [PDF]

				W. E. Mitch Insights into the Abnormalities of Chronic Renal Disease Attributed to Malnutrition J. Am. Soc. Nephrol., January 1, 2002; 13(90001): S22 - 27. [Abstract] [Full Text] [PDF]

				P. G. Boelens, R. J. Nijveldt, A. P. J. Houdijk, S. Meijer, and P. A. M. van Leeuwen Glutamine Alimentation in Catabolic State J. Nutr., September 1, 2001; 131(9): 2569S - 2577. [Abstract] [Full Text] [PDF]

				M. H. Porter, B. J. Hrupka, G. Altreuther, M. Arnold, and W. Langhans Inhibition of TNF-alpha production contributes to the attenuation of LPS-induced hypophagia by pentoxifylline Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2000; 279(6): R2113 - R2120. [Abstract] [Full Text] [PDF]

				R. Cooney, S. R. Kimball, R. Eckman, G. Maish III, M. Shumate, and T. C. Vary TNF-binding protein ameliorates inhibition of skeletal muscle protein synthesis during sepsis Am J Physiol Endocrinol Metab, April 1, 1999; 276(4): E611 - E619. [Abstract] [Full Text] [PDF]

				D. Breuille, L. Voisin, M. Contrepois, M. Arnal, F. Rose, and C. Obled A Sustained Rat Model for Studying the Long-Lasting Catabolic State of Sepsis Infect. Immun., March 1, 1999; 67(3): 1079 - 1085. [Abstract] [Full Text] [PDF]

				S. H. Lecker, V. Solomon, W. E. Mitch, and A. L. Goldberg Muscle Protein Breakdown and the Critical Role of the Ubiquitin-Proteasome Pathway in Normal and Disease States J. Nutr., January 1, 1999; 129(1): 227S - 227S. [Full Text] [PDF]

				L. Voisin, D. Breuille, B. Ruot, C. Ralliere, F. Rambourdin, M. Dalle, and C. Obled Cytokine modulation by PX differently affects specific acute phase proteins during sepsis in rats Am J Physiol Regulatory Integrative Comp Physiol, November 1, 1998; 275(5): R1412 - R1419. [Abstract] [Full Text] [PDF]

				T. C. Vary, D. Dardevet, J. Grizard, L. Voisin, C. Buffiere, P. Denis, D. Breuille, and C. Obled Differential regulation of skeletal muscle protein turnover by insulin and IGF-I after bacteremia Am J Physiol Endocrinol Metab, October 1, 1998; 275(4): E584 - E593. [Abstract] [Full Text] [PDF]

				W. E. Mitch and A. L. Goldberg Mechanisms of Muscle Wasting -- The Role of the Ubiquitin-Proteasome Pathway N. Engl. J. Med., December 19, 1996; 335(25): 1897 - 1905. [Full Text] [PDF]