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


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.


CONCLUSIONS
Increasing airflow obstruction and hypercapnia are associated with an enhanced TNFalpha response in COPD.
von Haehling
Stephan
S
Department of Medicine II, Johannes Gutenberg-University, Mainz, Germany.
Hopkinson
Nicholas S
NS
Polkey
Michael I
MI
Niethammer
Margit
M
Anker
Stefan D
SD
Genth-Zotz
Sabine
S
D000368:Aged; D016207:Cytokines / Q000097:blood; D004185:Disability Evaluation; D018450:Disease Progression; D004731:Endotoxins / Q000097:blood; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D029424:Pulmonary Disease, Chronic Obstructive / Q000145:classification / Q000175:diagnosis / Q000276:immunology*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D012016:Reference Values; D012129:Respiratory Function Tests; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
D016207:Cytokines; D004731:Endotoxins; D008070:Lipopolysaccharides; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha