ELEVATED TNF-ALPHA PRODUCTION BY PERIPHERAL-BLOOD MONOCYTES OF WEIGHT-LOSING COPD PATIENTS

The inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) an d interleukin-1-beta (IL-1 beta), have been associated with accelerate d metabolism and protein turnover following exogenous administration i n normal humans. We hypothesized that these inflammatory cytokines mig ht contribute to the weight-losing process in patients with chronic ob structive pulmonary disease (COPD). COPD patients were identified pros pectively as ''weight losers'' (WL; n = 10) if they reported > 5% weig ht loss during the preceding year or as ''weight stable'' (WS; n = 10) if their body weight fluctuated less than or equal to 5%. Age-matched healthy volunteers were selected as the control group (C; n = 13). Mo nocytes were isolated from a peripheral blood sample, cultured, and ex posed to lipopolysaccharide (LPS). The concentration of TNF-alpha and IL-1 beta in the monocyte supernatant was measured using a four layer enhanced ELISA. No significant difference in LPS-stimulated IL-1 beta production was found in the three study populations. However, LPS-stim ulated TNF-alpha production (mean [range] ng/ml) by monocytes was sign ificantly higher in the WL COPD patients (20.2 [6.3 to 44.8]), compare d 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 absenc e of ongoing weight loss. Definition of a causal relationship between TNF-alpha production and weight loss will require further understandin g of the relationship between energy metabolism and TNF-alpha producti on in these patients.