title: The relationship between chronic hypoxemia and activation of the tumor necrosis factor-alpha system in patients with chronic obstructive pulmonary disease.
abstract: Although circulating tumor necrosis factor (TNF)-alpha 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 TNF-alpha in vitro, we studied the relationship between hypoxemia and activities of the TNF-alpha system, including circulating TNF-alpha and soluble TNF-receptors (sTNF-R; sTNF-R55 and -R75) levels, in 27 COPD patients and 15 age-matched healthy controls. The COPD patients showed a significant weight loss (body mass index = 18.1 +/- 2.8 versus 22.8 +/- 2.2 [mean +/- SD] kg/m(2); p < 0.0001. % fat = 16.3 +/- 5.9 versus 24.3 +/- 4.9 %; p < 0.001), and hypoxemia (Pa(O2 )= 62.2 +/- 9.5 versus 88.6 +/- 5.9 mm Hg; p < 0.0001) as compared with the healthy controls. Serum TNF-alpha (6.15 +/- 1.08 versus 5.41 +/- 1.60 pg/ml; p < 0.05) and plasma sTNF-R55 (1.15 +/- 0.49 versus 0.67 +/- 0.13 ng/ml; p < 0.0001) and sTNF-R75 (3.54 +/- 1.16 versus 2.25 +/- 0.43; p < 0.0001) levels were significantly higher in the COPD patients than in the healthy controls. There were inverse correlations between Pa(O(2)) and circulating TNF-alpha and sTNF-R levels in patients with COPD (TNF-alpha; r = -0.426, p = 0.0297; sTNF-R55: r = -0.587, p = 0.0027; sTNF-R75: r = -0.573, p = 0.0035). In addition, we found inverse correlations between sTNF-R levels and % fat in COPD patients (sTNF-R55: r = -0.442, p = 0.0272; sTNF-R75: r = -0. 484, p = 0.0155). TNF-alpha levels correlated well with sTNF-R levels (sTNF-R55: r = 0.488, p = 0.0127; sTNF-R75: r = 0.609, p = 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 TNF-alpha system in vivo, which may be a factor contributing to the weight loss in patients with the disease.
authors.affiliation: First Department of Internal Medicine, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Takabatake
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: S
authors.initials: S
authors.lastname: Abe
authors.forename: S
authors.initials: S
authors.lastname: Inoue
authors.forename: T
authors.initials: T
authors.lastname: Hino
authors.forename: H
authors.initials: H
authors.lastname: Saito
authors.forename: H
authors.initials: H
authors.lastname: Yuki
authors.forename: S
authors.initials: S
authors.lastname: Kato
authors.forename: H
authors.initials: H
authors.lastname: Tomoike
mesh_terms: D000368:Aged; D002100:Cachexia / Q000503:physiopathology; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D008173:Lung Diseases, Obstructive / Q000097:blood / Q000503:physiopathology*; D008297:Male; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015431:Weight Loss
chemical_list: D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha