An increase of soluble Fas, an inhibitor of apoptosis, associated with progression of COPD

Abstract

In chronic obstructive pulmonary disease (COPD) which consists of emphysema and chronic bronchitis, alveolar tissue and/or bronchiolar walls are progressively destroyed. This suggests cell death by necrosis and/or apoptosis although no direct evidence of apoptosis has been reported. It was speculated that the apoptosis-related factors are associated with the progression of COPD. Fas/Apo-1 receptor (Fas), Fas ligand (Fas-L) and soluble Fas ligand (sFas-L) are inducers, while soluble Fas (sFas) is an inhibitor of apoptosis. In this study, plasma sFas and sFas-L were measured in 19 COPD patients receiving supplemental O2 (severe COPD) and 20 COPD patients not receiving supplemental O2 (mild/moderate COPD). Twenty-two age- and sex-matched healthy volunteers (healthy controls) and 20 patients receiving supplemental O2 and with level of hypoxaemia similar to severe COPD due to other pulmonary diseases (disease controls) were also examined. Plasma sFas-L was within normal limits in all groups. Plasma sFas levels were similar among healthy controls, disease controls, and mild/moderate COPD patients, but significantly increased in severe COPD (2.6 +/- 1.1, 2.6 +/- 0.2, 2.8 +/- 0.2 and 4.8 +/- 1.0 ng ml-1, respectively). Although PaO2 was lower in severe COPD than in mild/moderate COPD, and PaCO2 was higher in severe COPD than in mild/moderate COPD, they were close between severe COPD and disease controls. Tumour necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6) and C-reactive protein (CRP) were increased in patients with COPD, but were similar in both severe and mild/moderate COPD patients. We conclude that increased plasma sFas, which is independent of hypoxaemia, and increases in PaCO2, TNF-alpha, IL-6 and inflammation, may be associated with progression of COPD.

Cytokines and dietary energy restriction in stable chronic obstructive pulmonary disease patients

“…In these patients, the prevalence of nutritional depletion, a dietary intake significantly higher than estimated energy needs and evidence suggesting ongoing inflammatory reaction, as shown by the finding of higher serum IL-6 concentration, are in agreement with previously available data obtained in clinically stable COPD patients [1,[17][18][19][20]. Although no significant relationship could be established, these findings may indicate that the higher levels of IL-6 are not related to a deficit of energy intake and that other factors may contribute to the elevated levels of this cytokine in COPD patients.…”

Accuracy of symptoms, signs, and C-reactive protein for early chronic obstructive pulmonary disease

“…The univariable relation between elevated CRP level and COPD in the study data confirms previous studies reporting higher CRP-values in (known) COPD, 7,8,31,32 of which some considered high-sensitive CRP measurements (allowing for measurement of CRP level <3 mg/l). 7,31 Some of these studies compared COPD cases with their age-and sex-matched controls, 8,31 suggesting that the relationship was not caused by different age or sex distributions in COPD.…”

“…7,31 Some of these studies compared COPD cases with their age-and sex-matched controls, 8,31 suggesting that the relationship was not caused by different age or sex distributions in COPD. One study found that the higher CRP level in COPD was independent of smoking, and that CRP was lower in patients with COPD who used inhaled steroids.…”

Severity of Elastase-Induced Emphysema Is Decreased in Tumor Necrosis Factor-α and Interleukin-1β Receptor-Deficient Mice

“…Increases in the levels of the proapoptotic factor soluble Fas was reported in patients with chronic obstructive pulmonary disease (Yasuda et al, 1998). We found increases in apoptotic cells in the alveolar wall in elastasetreated mice at 5 days after injury.…”