Elevated TNFalpha production in whole blood in patients with severe COPD: the potential link to disease severity

Wien Klin Wochenschr. 2009;121(9-10):303-8. doi: 10.1007/s00508-009-1186-7.


Objective: The relationship between tumour necrosis factor-alpha (TNFalpha), severity of pulmonary disease and nutritional depletion in chronic obstructive pulmonary disease (COPD) remains unclear. We aimed to clarify the role of lipopolysaccharide (LPS) as a potential stimulus of cytokine production and the role of these cytokines in the alteration of body composition in patients with different degrees of COPD.

Patients and methods: We studied 29 weight-stable out-patients with different severites of COPD who had no evidence of recent infection or significant co-morbidity. Baseline serum TNFalpha levels and TNFalpha response to LPS in whole blood were measured in patients and 20 aged matched controls.

Results: Serum TNFalpha was significantly elevated in patients versus controls (2.1 +/- 0.3 vs. 1.1 +/- 0.1 pg/ml, mean +/- SEM, P = 0.007). In patients with COPD, we found a significant correlation between serum TNFalpha levels and disease severity, assessed as FEV(1) %predicted (r = 0.49, P = 0.02). Response to lipopolysaccharide did not differ significantly between patients and controls. However, within the patient group those with more severe disease (FEV(1) < or = 30% predicted, n = 12) had an enhanced response compared to patients with mild-to-moderate disease (all P < 0.05 for LPS > 1 ng/ml). Spontaneous TNFalpha production was 5.0 times higher in patients with severe COPD compared to mild-to-moderate COPD (P = 0.02). There was no relation between body composition and serum TNFalpha or TNFalpha response to LPS.

Conclusion: Increasing airflow obstruction and hypercapnia are associated with an enhanced TNFalpha response in COPD.

MeSH terms

  • Aged
  • Cytokines / blood
  • Disability Evaluation
  • Disease Progression
  • Endotoxins / blood
  • Female
  • Humans
  • Lipopolysaccharides / immunology
  • Male
  • Middle Aged
  • Prognosis
  • Pulmonary Disease, Chronic Obstructive / classification
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / immunology*
  • Receptors, Tumor Necrosis Factor, Type II / blood
  • Reference Values
  • Respiratory Function Tests
  • Tumor Necrosis Factor-alpha / blood*


  • Cytokines
  • Endotoxins
  • Lipopolysaccharides
  • Receptors, Tumor Necrosis Factor, Type II
  • Tumor Necrosis Factor-alpha