Elevated TNFα production in whole blood in patients with severe COPD: the potential link to disease severity
OBJECTIVE: The relationship between tumour necrosis factor-α (TNFα), 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 TNFα levels and TNFα response to LPS in whole blood were measured in patients and 20 aged matched controls. RESULTS: Serum TNFα 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 TNFα levels and disease severity, assessed as FEV1 %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 (FEV1 ≤ 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 TNFα 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 TNFα or TNFα response to LPS. CONCLUSION: Increasing airflow obstruction and hypercapnia are associated with an enhanced TNFα response in COPD.