Increased tumour necrosis factor‐α plasma levels during moderate-intensity exercise in COPD patients

Abstract

Post-training downregulation of muscle tumour necrosis factor (TNF)-a messenger ribonucleic acid (mRNA) expression and decrease in cellular TNF-a levels have been reported in the elderly. It is hypothesised that chronic obstructive pulmonary disease (COPD) patients may not show these adaptations due to their reduced ability to increase muscle antioxidant capacity with training.Eleven COPD patients (forced expiratory volume in one second 40¡4.4% of the predicted value) and six age-matched controls were studied. Pre-and post-training levels of TNF-a, soluble TNF receptors (sTNFRs: sTNFR55 and sTNFR75) and interleukin (IL)-6 in plasma at rest and during exercise and vastus lateralis TNF-a mRNA were examined.Moderate-intensity constant-work-rate exercise (11 min at 40% of pretraining peak work-rate) increased pretraining plasma TNF-a levels in COPD patients (from 17 ¡ 3.2 to 23¡2.7 pg?mL -1 ; pv0.005) but not in controls (from 19¡4.6 to 19¡3.2 pg?mL -1 ). No changes were observed in sTNFRs or IL-6 levels. After 8 weeks9 endurance training, moderate-intensity exercise increased plasma TNF-a levels similarly to pretraining (from 16¡3 to 21¡4 pg?mL -1 ; pv0.01). Pretraining muscle TNF-a mRNA expression was significantly higher in COPD patients than in controls (29.3¡13.9 versus 5.0¡1.5 TNF-a/18S ribonucleic acid, respectively), but no changes were observed after exercise or training.It is concluded that moderate-intensity exercise abnormally increases plasma tumour necrosis factor-a levels in chronic obstructive pulmonary disease patients without exercise-induced upregulation of the tumour necrosis factor-a gene in skeletal muscle. Eur Respir J 2003; 21: 789-794.

Skeletal muscle inflammation and nitric oxide in patients with COPD

“…This is in agreement with the findings reported by RABINOVICH et al [27], who studied nine patients and six healthy controls and found that at rest, TNF-a mRNA expression was significantly higher in the COPD patients.…”

Do COPD and Healthy Subjects have Similar Acute Inflammatory Response Induced by Sub-maximum Effort Test?

“…However, other studies, with more consistence methodology, perceived this difference [2,32]. As opposed to the present study, it was verified in COPD individuals and increase in TNF-α plasma levels after eleven minutes of moderate intensity ergometric exercise [8]. The present study, in turn, although the mean was numerically higher after 6MWT in COPD group, verified no significant difference.…”

“…To be able to detect a 10% difference or higher between the means of both groups, regarding the utilization of a proportion of 1 control to 2 individuals with COPD commonly employed in the literature [8], the sample calculation showed the need to include 17 individuals in the COPD group and 8 individuals in the control group. It was decided to include 20% more individuals in the COPD group due to the risk of losses throughout the study.…”

“…Even outside the clinical decompensation period and in rest, there are high levels of inflammatory cells, cytokines and acute phase proteins in these individuals' peripheral blood, being the main Interleukin 6 (IL-6), a interleukin 8 (IL-8), tumoral necrosis factor alfa (TNF-α) and Creactive protein (CRP) [3,4]. Physical exercise, depending on its intensity, duration and muscular mass involved, is capable of provoking an increase in oxidative stress and inflammatory biomarkers levels in healthy individuals' peripheral blood [5,6] and in COPD carriers [7,8]. According to Van Helvoort et al [9], after maximum exercise, in COPD patients, there is a significant increase of leukocytes in peripheral blood.…”

Mechanisms of atherothrombosis in chronic obstructive pulmonary disease

“…Accordingly, systemic blood concentrations of tumor necrosis factor (TNF)-α, IL 6, IL 8, CRP and fi brinogen are higher in COPD than in control subjects (Gan et al 2004). Interestingly, at variance from the response observed in healthy subjects and diabetic patients, moderate-intensity exercise abnormally increases plasma TNF-α levels in COPD patients (Rabinovich et al 2003;Zoppini et al 2006). Circulating TNF-α levels have been found to increase in malnourished COPD patients, likely because systemic hypoxia stimulates TNF-α synthesis (Takabatake et al 2000).…”