The Relationship between Chronic Hypoxemia and Activation of the Tumor Necrosis Factor- a System in Patients with Chronic Obstructive Pulmonary Disease

Although circulating tumor necrosis factor (TNF)a levels have been found to be increased in weight-losing patients with chronic obstructive pulmonary disease (COPD), the main causes for this phenomenon remain to be elucidated. Since hypoxia itself can enhance the production of the TNFa in vitro , we studied the relationship between hypoxemia and activities of the TNFa system, including circulating TNFa and soluble TNF-receptors (sTNF-R; sTNF-R55 and -R75) levels, in 27 COPD patients and 15 agematched healthy controls. The COPD patients showed a significant weight loss (body mass index 5 18.1 6 2.8 versus 22.8 6 2.2 [mean 6 SD] kg/m 2 ; p , 0.0001. % fat 5 16.3 6 5.9 versus 24.3 6 4.9 %; p , 0.001), and hypoxemia (Pa O2 5 62.2 6 9.5 versus 88.6 6 5.9 mm Hg; p , 0.0001) as compared with the healthy controls. Serum TNFa (6.15 6 1.08 versus 5.41 6 1.60 pg/ml; p , 0.05) and plasma sTNF-R55 (1.15 6 0.49 versus 0.67 6 0.13 ng/ml; p , 0.0001) and sTNF-R75 (3.54 6 1.16 versus 2.25 6 0.43; p , 0.0001) levels were significantly higher in the COPD patients than in the healthy controls. There were inverse correlations between Pa O2 and circulating TNFa and sTNF-R levels in patients with COPD (TNFa ; r 5 2 0.426, p 5 0.0297; sTNF-R55: r 5 2 0.587, p 5 0.0027; sTNF-R75: r 5 2 0.573, p 5 0.0035). In addition, we found inverse correlations between sTNF-R levels and % fat in COPD patients (sTNFR55: r 5 2 0.442, p 5 0.0272; sTNF-R75: r 5 2 0.484, p 5 0.0155). TNFa levels correlated well with sTNF-R levels (sTNF-R55: r 5 0.488, p 5 0.0127; sTNF-R75: r 5 0.609, p 5 0.0019). These relationships were not observed in the healthy controls. These data suggest that systemic hypoxemia noted in patients with COPD is associated with activation of the TNFa system in vivo , which may be a factor contributing to the weight loss in patients with the disease.