M Di Francia, D Barbier, JL Mege and J Orehek
Departement des Maladies Respiratoires, Hopital Sainte Marguerite, Marseille, France.

Unexplained weight loss is common in chronic obstructive pulmonary disease (COPD). Blood levels of tumor necrosis factor-alpha (TNF- alpha), a cytokine causing cachexia in laboratory animals, are elevated in various human diseases associated with weight loss. We therefore prospectively measured TNF-alpha serum levels (immunoradiometric assay) in patients with clinically stable COPD (n = 30; all male; mean age, 65 yr) whose weight was less (Group I; n = 16) or more (Group II; n = 14) than the lower limit of normal taken from Metropolitan Life Insurance Company tables. The patients had no cause known to elevate TNF-alpha serum levels; notably, they were not infected. Group I patients had unintentionally lost weight during the previous year, whereas the weight of Group II patients had not changed during the same period. The two groups had similar chronic airflow obstruction and arterial blood gas impairment; hyperinflation and reduction in diffusing capacity were more pronounced in Group I, but differences were not significant. TNF- alpha serum levels (pg/ml; mean [SD]) were significantly higher in Group I than in Group II (70.2 [100.0] versus 6.7 [6.4]; p < 0.001). Group II TNF-alpha serum levels did not differ significantly from those of healthy subjects (7.8 [3.9]), whereas those of Group I were significantly higher (p < 0.001). Because renal function was in the normal range, we conclude that increased TNF-alpha production--and not decreased TNF-alpha clearance--is a likely cause of weight loss in patients with COPD.

This article has been cited by other articles:

				D. A. King, F. Cordova, and S. M. Scharf Nutritional Aspects of Chronic Obstructive Pulmonary Disease Proceedings of the ATS, May 1, 2008; 5(4): 519 - 523. [Abstract] [Full Text] [PDF]

				P. D. Wagner Possible mechanisms underlying the development of cachexia in COPD Eur. Respir. J., March 1, 2008; 31(3): 492 - 501. [Abstract] [Full Text] [PDF]

				M. Cazzola, W. MacNee, F. J. Martinez, K. F. Rabe, L. G. Franciosi, P. J. Barnes, V. Brusasco, P. S. Burge, P. M. A. Calverley, B. R. Celli, et al. Outcomes for COPD pharmacological trials: from lung function to biomarkers Eur. Respir. J., February 1, 2008; 31(2): 416 - 469. [Abstract] [Full Text] [PDF]

				E Barreiro, A M W J Schols, M I Polkey, J B Galdiz, H R Gosker, E B Swallow, C Coronell, J Gea, and on behalf of the ENIGMA in COPD project Cytokine profile in quadriceps muscles of patients with severe COPD Thorax, February 1, 2008; 63(2): 100 - 107. [Abstract] [Full Text] [PDF]

				C. Casadevall, C. Coronell, A. L. Ramirez-Sarmiento, J. Martinez-Llorens, E. Barreiro, M. Orozco-Levi, J. Gea, and on behalf of the ENIGMA in COPD group Upregulation of pro-inflammatory cytokines in the intercostal muscles of COPD patients Eur. Respir. J., October 1, 2007; 30(4): 701 - 707. [Abstract] [Full Text] [PDF]

				A. H. Remels, P. Schrauwen, R. Broekhuizen, J. Willems, S. Kersten, H. R. Gosker, and A. M. Schols Peroxisome proliferator-activated receptor expression is reduced in skeletal muscle in COPD Eur. Respir. J., August 1, 2007; 30(2): 245 - 252. [Abstract] [Full Text] [PDF]

				K. Tomoda, M. Yoshikawa, T. Itoh, S. Tamaki, A. Fukuoka, K. Komeda, and H. Kimura Elevated Circulating Plasma Adiponectin in Underweight Patients With COPD Chest, July 1, 2007; 132(1): 135 - 140. [Abstract] [Full Text] [PDF]

				C. A. C. Ottenheijm, L. M. A. Heunks, and P. N. R. Dekhuijzen Diaphragm Muscle Fiber Dysfunction in Chronic Obstructive Pulmonary Disease: Toward a Pathophysiological Concept Am. J. Respir. Crit. Care Med., June 15, 2007; 175(12): 1233 - 1240. [Abstract] [Full Text] [PDF]

				J. Vestbo Systemic inflammation and progression of COPD Thorax, June 1, 2007; 62(6): 469 - 470. [Full Text] [PDF]

				S. I. Rennard, C. Fogarty, S. Kelsen, W. Long, J. Ramsdell, J. Allison, D. Mahler, C. Saadeh, T. Siler, P. Snell, et al. The Safety and Efficacy of Infliximab in Moderate to Severe Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., May 1, 2007; 175(9): 926 - 934. [Abstract] [Full Text] [PDF]

				C. E Bolton, R. Broekhuizen, A. A Ionescu, L. S Nixon, E. F M Wouters, D. J Shale, and A. M W J Schols Cellular protein breakdown and systemic inflammation are unaffected by pulmonary rehabilitation in COPD Thorax, February 1, 2007; 62(2): 109 - 114. [Abstract] [Full Text] [PDF]

				D. D. Sin, N. R. Anthonisen, J. B. Soriano, and A. G. Agusti Mortality in COPD: role of comorbidities Eur. Respir. J., December 1, 2006; 28(6): 1245 - 1257. [Abstract] [Full Text] [PDF]

				R. C. J. Langen, A. M. W. J. Schols, M. C. J. M. Kelders, J. L. J. van der Velden, E. F. M. Wouters, and Y. M. W. Janssen-Heininger Muscle Wasting and Impaired Muscle Regeneration in a Murine Model of Chronic Pulmonary Inflammation Am. J. Respir. Cell Mol. Biol., December 1, 2006; 35(6): 689 - 696. [Abstract] [Full Text] [PDF]

				P. M. Henson, R. W. Vandivier, and I. S. Douglas Cell Death, Remodeling, and Repair in Chronic Obstructive Pulmonary Disease? Proceedings of the ATS, November 1, 2006; 3(8): 713 - 717. [Abstract] [Full Text] [PDF]

				S. Jelic and T. H. Le Jemtel Diagnostic Usefulness of B-Type Natriuretic Peptide and Functional Consequences of Muscle Alterations in COPD and Chronic Heart Failure. Chest, October 1, 2006; 130(4): 1220 - 1230. [Abstract] [Full Text] [PDF]

				B. R. Celli Roger S. Mitchell Lecture. Chronic Obstructive Pulmonary Disease Phenotypes and Their Clinical Relevance Proceedings of the ATS, August 1, 2006; 3(6): 461 - 465. [Abstract] [Full Text] [PDF]

				A. I. D'hulst, K. R. Bracke, T. Maes, J. L. De Bleecker, R. A. Pauwels, G. F. Joos, and G. G. Brusselle Role of tumour necrosis factor-{alpha} receptor p75 in cigarette smoke-induced pulmonary inflammation and emphysema Eur. Respir. J., July 1, 2006; 28(1): 102 - 112. [Abstract] [Full Text] [PDF]

				M A Dentener, R Louis, R H E Cloots, M Henket, and E F M Wouters Differences in local versus systemic TNF{alpha} production in COPD: inhibitory effect of hyaluronan on LPS induced blood cell TNF{alpha} release Thorax, June 1, 2006; 61(6): 478 - 484. [Abstract] [Full Text] [PDF]

				T. Similowski, A. Agusti, W. MacNee, and B. Schonhofer The potential impact of anaemia of chronic disease in COPD Eur. Respir. J., February 1, 2006; 27(2): 390 - 396. [Abstract] [Full Text] [PDF]

				J. Vestbo, E. Prescott, T. Almdal, M. Dahl, B. G. Nordestgaard, T. Andersen, T. I. A. Sorensen, and P. Lange Body Mass, Fat-Free Body Mass, and Prognosis in Patients with Chronic Obstructive Pulmonary Disease from a Random Population Sample: Findings from the Copenhagen City Heart Study Am. J. Respir. Crit. Care Med., January 1, 2006; 173(1): 79 - 83. [Abstract] [Full Text] [PDF]

				R Broekhuizen, E F M Wouters, E C Creutzberg, and A M W J Schols Raised CRP levels mark metabolic and functional impairment in advanced COPD Thorax, January 1, 2006; 61(1): 17 - 22. [Abstract] [Full Text] [PDF]

				M. A. Spruit, R. Gosselink, T. Troosters, A. Kasran, M. Van Vliet, and M. Decramer Low-Grade Systemic Inflammation and the Response to Exercise Training in Patients With Advanced COPD Chest, November 1, 2005; 128(5): 3183 - 3190. [Abstract] [Full Text] [PDF]

				M. I. Lewis, X. Da, H. Li, and M. Fournier Tumor necrosis factor-{alpha} and malnutrition-induced inhibition of diaphragm fiber growth in young rats J Appl Physiol, November 1, 2005; 99(5): 1649 - 1657. [Abstract] [Full Text] [PDF]

				A. Couillard and C. Prefaut From muscle disuse to myopathy in COPD: potential contribution of oxidative stress Eur. Respir. J., October 1, 2005; 26(4): 703 - 719. [Abstract] [Full Text] [PDF]

				G. C. Donaldson, T. A. R. Seemungal, I. S. Patel, A. Bhowmik, T. M. A. Wilkinson, J. R. Hurst, P. K. MacCallum, and J. A. Wedzicha Airway and Systemic Inflammation and Decline in Lung Function in Patients With COPD Chest, October 1, 2005; 128(4): 1995 - 2004. [Abstract] [Full Text] [PDF]

				H. Bruunsgaard Physical activity and modulation of systemic low-level inflammation J. Leukoc. Biol., October 1, 2005; 78(4): 819 - 835. [Abstract] [Full Text] [PDF]

				A. Chambellan, E. Chailleux, and T. Similowski Prognostic Value of the Hematocrit in Patients With Severe COPD Receiving Long-term Oxygen Therapy Chest, September 1, 2005; 128(3): 1201 - 1208. [Abstract] [Full Text] [PDF]

				H. van der Vaart, G. H. Koeter, D. S. Postma, H. F. Kauffman, and N. H. T. ten Hacken First Study of Infliximab Treatment in Patients with Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., August 15, 2005; 172(4): 465 - 469. [Abstract] [Full Text] [PDF]

				C. A. C. Ottenheijm, L. M. A. Heunks, G. C. Sieck, W.-Z. Zhan, S. M. Jansen, H. Degens, T. de Boo, and P. N. R. Dekhuijzen Diaphragm Dysfunction in Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., July 15, 2005; 172(2): 200 - 205. [Abstract] [Full Text] [PDF]

				R Broekhuizen, E F M Wouters, E C Creutzberg, C A P M Weling-Scheepers, and A M W J Schols Polyunsaturated fatty acids improve exercise capacity in chronic obstructive pulmonary disease Thorax, May 1, 2005; 60(5): 376 - 382. [Abstract] [Full Text] [PDF]

				E. F. M. Wouters Local and Systemic Inflammation in Chronic Obstructive Pulmonary Disease Proceedings of the ATS, April 1, 2005; 2(1): 26 - 33. [Abstract] [Full Text] [PDF]

				W. MacNee Pulmonary and Systemic Oxidant/Antioxidant Imbalance in Chronic Obstructive Pulmonary Disease Proceedings of the ATS, April 1, 2005; 2(1): 50 - 60. [Abstract] [Full Text] [PDF]

				S. F. van Eeden, A. Yeung, K. Quinlam, and J. C. Hogg Systemic Response to Ambient Particulate Matter: Relevance to Chronic Obstructive Pulmonary Disease Proceedings of the ATS, April 1, 2005; 2(1): 61 - 67. [Abstract] [Full Text] [PDF]

				S. I. Rennard Clinical Approach to Patients with Chronic Obstructive Pulmonary Disease and Cardiovascular Disease Proceedings of the ATS, April 1, 2005; 2(1): 94 - 100. [Abstract] [Full Text] [PDF]

				S. D. Nathan Lung Transplantation: Disease-Specific Considerations for Referral Chest, March 1, 2005; 127(3): 1006 - 1016. [Abstract] [Full Text] [PDF]

				G. C. Donaldson, T. M. A. Wilkinson, J. R. Hurst, W. R. Perera, and J. A. Wedzicha Exacerbations and Time Spent Outdoors in Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., March 1, 2005; 171(5): 446 - 452. [Abstract] [Full Text] [PDF]

				A. Mallampalli Nutritional Management of the Patient With Chronic Obstructive Pulmonary Disease Nutr Clin Pract, December 1, 2004; 19(6): 550 - 556. [Abstract] [Full Text] [PDF]

				P. J. Barnes Mediators of Chronic Obstructive Pulmonary Disease Pharmacol. Rev., December 1, 2004; 56(4): 515 - 548. [Abstract] [Full Text] [PDF]

				R. Casaburi, S. Bhasin, L. Cosentino, J. Porszasz, A. Somfay, M. I. Lewis, M. Fournier, and T. W. Storer Effects of Testosterone and Resistance Training in Men with Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., October 15, 2004; 170(8): 870 - 878. [Abstract] [Full Text] [PDF]

				E. Ardite, J. A. Barbera, J. Roca, and J. C. Fernandez-Checa Glutathione Depletion Impairs Myogenic Differentiation of Murine Skeletal Muscle C2C12 Cells through Sustained NF-{kappa}B Activation Am. J. Pathol., September 1, 2004; 165(3): 719 - 728. [Abstract] [Full Text] [PDF]

				M. R. Mazan, E. F. Deveney, S. DeWitt, D. Bedenice, and A. Hoffman Energetic cost of breathing, body composition, and pulmonary function in horses with recurrent airway obstruction J Appl Physiol, July 1, 2004; 97(1): 91 - 97. [Abstract] [Full Text] [PDF]

				W Q Gan, S F P Man, A Senthilselvan, and D D Sin Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis Thorax, July 1, 2004; 59(7): 574 - 580. [Abstract] [Full Text] [PDF]

				C. Koechlin, A. Couillard, J.P. Cristol, P. Chanez, M. Hayot, D. Le Gallais, and C. Prefaut Does systemic inflammation trigger local exercise-induced oxidative stress in COPD? Eur. Respir. J., April 1, 2004; 23(4): 538 - 544. [Abstract] [Full Text] [PDF]

				R. C. J. LANGEN, J. L. J. VAN DER VELDEN, A. M. W. J. SCHOLS, M. C. J. M. KELDERS, E. F. M. WOUTERS, and Y. M. W. JANSSEN-HEININGER Tumor necrosis factor-alpha inhibits myogenic differentiation through MyoD protein destabilization FASEB J, February 1, 2004; 18(2): 227 - 237. [Abstract] [Full Text] [PDF]

				I. Godoy, A.O. Campana, R.R.C. Geraldo, C.R. Padovani, and S.A.R Paiva Cytokines and dietary energy restriction in stable chronic obstructive pulmonary disease patients Eur. Respir. J., December 1, 2003; 22(6): 920 - 925. [Abstract] [Full Text] [PDF]

				M. Decramer Treatment of chronic respiratory failure: lung volume reduction surgery versus rehabilitation Eur. Respir. J., November 16, 2003; 22(47_suppl): 47S - 56s. [Abstract] [Full Text] [PDF]

				H. Andreassen and J. Vestbo Chronic obstructive pulmonary disease as a systemic disease: an epidemiological perspective Eur. Respir. J., November 2, 2003; 22(46_suppl): 2S - 4s. [Abstract] [Full Text] [PDF]

				A.A. Ionescu and E. Schoon Osteoporosis in chronic obstructive pulmonary disease Eur. Respir. J., November 2, 2003; 22(46_suppl): 64S - 75s. [Abstract] [Full Text] [PDF]

				R. I. Cohen, K. Marzouk, P. Berkoski, C. P. O'Donnell, V. Y. Polotsky, and S. M. Scharf Body Composition and Resting Energy Expenditure in Clinically Stable, Non-Weight-Losing Patients With Severe Emphysema Chest, October 1, 2003; 124(4): 1365 - 1372. [Abstract] [Full Text] [PDF]

				H.R. Gosker, B. Kubat, G. Schaart, G.J. van der Vusse, E.F.M. Wouters, and A.M.W.J. Schols Myopathological features in skeletal muscle of patients with chronic obstructive pulmonary disease Eur. Respir. J., August 1, 2003; 22(2): 280 - 285. [Abstract] [Full Text] [PDF]

				R.A. Rabinovich, M. Figueras, E. Ardite, N. Carbo, T. Troosters, X. Filella, J.A. Barbera, J.C. Fernandez-Checa, J.M. Argiles, and J. Roca Increased tumour necrosis factor-{alpha} plasma levels during moderate-intensity exercise in COPD patients Eur. Respir. J., May 1, 2003; 21(5): 789 - 794. [Abstract] [Full Text] [PDF]

				I. Ferrarotti, M. Zorzetto, M. Beccaria, L.S. Gile, R. Porta, N. Ambrosino, P.F. Pignatti, I. Cerveri, E. Pozzi, and M. Luisetti Tumour necrosis factor family genes in a phenotype of COPD associated with emphysema Eur. Respir. J., March 1, 2003; 21(3): 444 - 449. [Abstract] [Full Text] [PDF]

				A.G.N. Agusti, A. Noguera, J. Sauleda, E. Sala, J. Pons, and X. Busquets Systemic effects of chronic obstructive pulmonary disease Eur. Respir. J., February 1, 2003; 21(2): 347 - 360. [Abstract] [Full Text] [PDF]

				H. Katsura and K. Kida A Comparison of Bone Mineral Density in Elderly Female Patients With COPD and Bronchial Asthma Chest, December 1, 2002; 122(6): 1949 - 1955. [Abstract] [Full Text] [PDF]

				E F M Wouters Chronic obstructive pulmonary disease * 5: Systemic effects of COPD Thorax, December 1, 2002; 57(12): 1067 - 1070. [Abstract] [Full Text] [PDF]

				J. H. Vernooy, M. Kucukaycan, J. A. Jacobs, N. H. Chavannes, W. A. Buurman, M. A. Dentener, and E. F. Wouters Local and Systemic Inflammation in Patients with Chronic Obstructive Pulmonary Disease: Soluble Tumor Necrosis Factor Receptors Are Increased in Sputum Am. J. Respir. Crit. Care Med., November 1, 2002; 166(9): 1218 - 1224. [Abstract] [Full Text] [PDF]

				R. C. J. Langen, A. M. W. J. Schols, M. C. J. M. Kelders, J. L. J. van der Velden, E. F. M. Wouters, and Y. M. W. Janssen-Heininger Tumor necrosis factor-alpha inhibits myogenesis through redox-dependent and -independent pathways Am J Physiol Cell Physiol, September 1, 2002; 283(3): C714 - C721. [Abstract] [Full Text] [PDF]

				M. B. Reid, J. Lannergren, and H. Westerblad Respiratory and Limb Muscle Weakness Induced by Tumor Necrosis Factor-{alpha}: Involvement of Muscle Myofilaments Am. J. Respir. Crit. Care Med., August 15, 2002; 166(4): 479 - 484. [Abstract] [Full Text] [PDF]

				E. F. M. Wouters, E. C. Creutzberg, and A. M. W. J. Schols Systemic Effects in COPD* Chest, May 1, 2002; 121(5_suppl): 127S - 130S. [Abstract] [Full Text] [PDF]

				R. DEBIGARE, C. H. COTE, and F. MALTAIS Peripheral Muscle Wasting in Chronic Obstructive Pulmonary Disease . Clinical Relevance and Mechanisms Am. J. Respir. Crit. Care Med., November 1, 2001; 164(9): 1712 - 1717. [Full Text] [PDF]

				A. A. EID, A. A. IONESCU, L. S. NIXON, V. LEWIS-JENKINS, S. B. MATTHEWS, T. L. GRIFFITHS, and D. J. SHALE Inflammatory Response and Body Composition in Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., October 15, 2001; 164(8): 1414 - 1418. [Abstract] [Full Text] [PDF]

				K.F. Chung Cytokines in chronic obstructive pulmonary disease Eur. Respir. J., July 2, 2001; 18(34_suppl): 50S - 59s. [Abstract] [Full Text] [PDF]

				G. Akner and T. Cederholm Treatment of protein-energy malnutrition in chronic nonmalignant disorders Am. J. Clinical Nutrition, July 1, 2001; 74(1): 6 - 24. [Abstract] [Full Text] [PDF]

R. C. J. LANGEN, A. M. W. J. SCHOLS, M. C. J. M. KELDERS, E. F. M. WOUTERS, and Y. M. W. JANSSEN-HEININGER Inflammatory cytokines inhibit myogenic differentiation through activation of nuclear factor-{kappa}B FASEB J, May 1, 2001; 15(7): 1169 - 1180. [Abstract] [Full Text] [PDF]