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Inflammatory response to exercise in COPD
ARTICLE IN PRESS Respiratory Medicine (2006) 100, 1125–1126
LETTER TO THE EDITOR Inflammatory response to exercise in COPD There is increasing recognition that chronic lowgrade inflammation is a feature of COPD, however, there are presently few papers evaluating the cytokine response to exercise. We were therefore interested in the stimulating work of van Helvoort et al.1 and would like to take this opportunity to raise a few thoughts. Systemic inflammation, in particular C-reactive protein is associated with cardiovascular mortality in healthy subjects2 and early work highlights possible similarities in COPD.3 van Helvoort et al.1 confirm the presence of raised CRP in COPD and demonstrate that systemic inflammation (as measured by circulating leukocytes and catecholamines) is markedly increased with acute exercise. However, in this study CRP levels were not raised after maximal exercise in healthy subjects nor in COPD patients. This finding is unexpected when one considers data from Rabinovich et al.4 showing raised levels of TNF alpha and Interleukin 6 (IL-6) after moderate intensity exercise in COPD patients. In healthy subjects IL-6 is the predominant cytokine released from muscle during exercise. IL-6 in turn appears to be the primary driver for CRP and is involved with regulation of TNF alpha with the effect of lowering TNF alpha via the presence of IL-1ra.5 Furthermore relationships between CRP and IL-6 have been demonstrated.6 The role of IL-6 seems so important in exercise in healthy subjects it has been termed the exercise ‘‘work factor’’ and is considered by our group to be a ‘‘fatigueogen’’ due to its impact on fatigue.7 We propose, in COPD, that elevated IL-6 concentrations may contribute to the early onset of fatigue and or breathlessness experienced during physical exercise.6 There is much debate concerning the type of muscle work, eccentric or concentric, and exercise, maximal or sub-maximal that provokes the greatest production of IL-6 but it is apparent that IL-6 increases exponentially with duration and intensity of exercise.5 van Helvoort et al. assessed levels of muscle damage after exercise and found
no evidence of such. It should be noted however, that in healthy subjects there is now strong evidence that IL-6 is produced locally by working skeletal muscle in the absence of muscle trauma and this fully accounts for the exercise-induced increase in plasma IL-6.8 We suggest that a one off bout of maximal exercise in COPD patients is insufficient to trigger an acute elevated cytokine response but that more prolonged endurance-type exercise may do so. We, like van Helvoort et al., agree this is an important area of work and recommend further studies are designed to define the exercise-induced cytokine response in COPD patients during different exercise strategies and modalities.
Reference 1. van Helvoort HA, van de Pol MH, Heijdra YF, Dekhuijzen PN. Systemic inflammatory response to exhaustive exercise in patients with chronic obstructive pulmonary disease. Respir Med 2005;99(12):1555–67. 2. Bassuk SS, Rifai N, Ridker PM. High-sensitivity C-reactive protein: clinical importance. Curr Probl Cardiol 2004;29(8): 439–93. 3. Sin DD, Man SF. Why are patients with chronic obstructive pulmonary disease at increased risk of cardiovascular diseases? The potential role of systemic inflammation in chronic obstructive pulmonary disease. Circulation 2003; 107(11):1514–9. 4. Rabinovich R, Figueras M, Ardite E, Carbo N, Troosters T, et al. Increased tumour necrosis factor alpha plasma levels during moderate-intensity exercise in COPD patients. Eur Respir J 2003;21:789–94. 5. Pedersen BK, Steensberg A, Fischer C, Keller C, Keller P, Plomgaard P, et al. The metabolic role of IL-6 produced during exercise: is IL-6 an exercise factor? Proc Nutr Soc 2004; 63(2):263–7. 6. Garrod R, Marshall J, Fredericks S, Hagan G. CRP as a marker of impairment and disability in chronic obstructive pulmonary disease (COPD). Proc Am Thoracic Soc 2005;2:A639. 7. Robson-Ansley PJ, de Milander L, Collins M, Noakes TD. Acute interleukin-6 administration impairs athletic performance in healthy, trained male runners. Can J Appl Physiol 2004;29(4): 411–8. 8. Steensberg A, Keller C, Starkie RL, Osada T, Febbraio MA, Pedersen BK. IL-6 and TNF-alpha expression in, and release from, contracting human skeletal muscle. Am J Physiol Endocrinol Metab 2002;283(6):E1272–8.
0954-6111/$ - see front matter & 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.rmed.2006.02.021
ARTICLE IN PRESS 1126 Jane Canavan, Rachel Garrod, Andy Jewell Faculty of Health and Social Care Sciences, St. George’s Hospital, University of London, Cranmer Terrace, Tooting, London, SW17 ORE, UK E-mail address: [email protected] (R. Garrod)
LETTER TO THE EDITOR Paula Robson-Ansley Department of Sport and Exercise Science, University of Portsmouth, St. Michael’s Building, White Swan Road, Portsmouth PO1 2DT, UK
LETTER TO THE EDITOR Inflammatory response to exercise in COPD There is increasing recognition that chronic lowgrade inflammation is a feature of COPD, however, there are presently few papers evaluating the cytokine response to exercise. We were therefore interested in the stimulating work of van Helvoort et al.1 and would like to take this opportunity to raise a few thoughts. Systemic inflammation, in particular C-reactive protein is associated with cardiovascular mortality in healthy subjects2 and early work highlights possible similarities in COPD.3 van Helvoort et al.1 confirm the presence of raised CRP in COPD and demonstrate that systemic inflammation (as measured by circulating leukocytes and catecholamines) is markedly increased with acute exercise. However, in this study CRP levels were not raised after maximal exercise in healthy subjects nor in COPD patients. This finding is unexpected when one considers data from Rabinovich et al.4 showing raised levels of TNF alpha and Interleukin 6 (IL-6) after moderate intensity exercise in COPD patients. In healthy subjects IL-6 is the predominant cytokine released from muscle during exercise. IL-6 in turn appears to be the primary driver for CRP and is involved with regulation of TNF alpha with the effect of lowering TNF alpha via the presence of IL-1ra.5 Furthermore relationships between CRP and IL-6 have been demonstrated.6 The role of IL-6 seems so important in exercise in healthy subjects it has been termed the exercise ‘‘work factor’’ and is considered by our group to be a ‘‘fatigueogen’’ due to its impact on fatigue.7 We propose, in COPD, that elevated IL-6 concentrations may contribute to the early onset of fatigue and or breathlessness experienced during physical exercise.6 There is much debate concerning the type of muscle work, eccentric or concentric, and exercise, maximal or sub-maximal that provokes the greatest production of IL-6 but it is apparent that IL-6 increases exponentially with duration and intensity of exercise.5 van Helvoort et al. assessed levels of muscle damage after exercise and found
no evidence of such. It should be noted however, that in healthy subjects there is now strong evidence that IL-6 is produced locally by working skeletal muscle in the absence of muscle trauma and this fully accounts for the exercise-induced increase in plasma IL-6.8 We suggest that a one off bout of maximal exercise in COPD patients is insufficient to trigger an acute elevated cytokine response but that more prolonged endurance-type exercise may do so. We, like van Helvoort et al., agree this is an important area of work and recommend further studies are designed to define the exercise-induced cytokine response in COPD patients during different exercise strategies and modalities.
Reference 1. van Helvoort HA, van de Pol MH, Heijdra YF, Dekhuijzen PN. Systemic inflammatory response to exhaustive exercise in patients with chronic obstructive pulmonary disease. Respir Med 2005;99(12):1555–67. 2. Bassuk SS, Rifai N, Ridker PM. High-sensitivity C-reactive protein: clinical importance. Curr Probl Cardiol 2004;29(8): 439–93. 3. Sin DD, Man SF. Why are patients with chronic obstructive pulmonary disease at increased risk of cardiovascular diseases? The potential role of systemic inflammation in chronic obstructive pulmonary disease. Circulation 2003; 107(11):1514–9. 4. Rabinovich R, Figueras M, Ardite E, Carbo N, Troosters T, et al. Increased tumour necrosis factor alpha plasma levels during moderate-intensity exercise in COPD patients. Eur Respir J 2003;21:789–94. 5. Pedersen BK, Steensberg A, Fischer C, Keller C, Keller P, Plomgaard P, et al. The metabolic role of IL-6 produced during exercise: is IL-6 an exercise factor? Proc Nutr Soc 2004; 63(2):263–7. 6. Garrod R, Marshall J, Fredericks S, Hagan G. CRP as a marker of impairment and disability in chronic obstructive pulmonary disease (COPD). Proc Am Thoracic Soc 2005;2:A639. 7. Robson-Ansley PJ, de Milander L, Collins M, Noakes TD. Acute interleukin-6 administration impairs athletic performance in healthy, trained male runners. Can J Appl Physiol 2004;29(4): 411–8. 8. Steensberg A, Keller C, Starkie RL, Osada T, Febbraio MA, Pedersen BK. IL-6 and TNF-alpha expression in, and release from, contracting human skeletal muscle. Am J Physiol Endocrinol Metab 2002;283(6):E1272–8.
0954-6111/$ - see front matter & 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.rmed.2006.02.021
ARTICLE IN PRESS 1126 Jane Canavan, Rachel Garrod, Andy Jewell Faculty of Health and Social Care Sciences, St. George’s Hospital, University of London, Cranmer Terrace, Tooting, London, SW17 ORE, UK E-mail address: [email protected] (R. Garrod)
LETTER TO THE EDITOR Paula Robson-Ansley Department of Sport and Exercise Science, University of Portsmouth, St. Michael’s Building, White Swan Road, Portsmouth PO1 2DT, UK