Elevated TNF-α production by peripheral blood monocytes of weight-losing COPD patients

The inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin-1-beta (IL-1β), have been associated with accelerated metabolism and protein turnover following exogenous administration in normal humans. We hypothesized that these inflammatory cytokines might contribute to the weight-losing process in patients with chronic obstructive pulmonary disease (COPD). COPD patients were identified prospectively as 'weight losers' (WL; n = 10) if they reported > 5% weight loss during the preceding year or as 'weight stable' (W5; n = 10) if their body weight fluctuated ≤ 5%. Age- matched healthy volunteers were selected as the control group (C; n = 13). Monocytes were isolated from a peripheral blood sample, cultured, and exposed to lipopolysaccharide (LPS). The concentration of TNF-α and IL-1β in the monocyte supernatant was measured using a four layer enhanced ELISA. No significant difference in LPS-stimulated IL-1β production was found in the three study populations. However, LPS-stimulated TNF-α production (mean [range] ng/ml) by monocytes was significantly higher in the WL COPD patients (20.2 [6.3 to 44.8]), compared with WS patients (6.9 [1.5 to 16.6]), and C subjects (5.7 [0 to 61.8]). This difference was not maintained at 6 mo follow-up in the absence of ongoing weight loss. Definition of a causal relationship between TNF-α production and weight loss will require further understanding of the relationship between energy metabolism and TNF-α production in these patients.