Elevated TNF-alpha production by peripheral blood monocytes of weight-losing COPD patients.
The inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1 beta), 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" (WS; n = 10) if their body weight fluctuated < or = 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-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-stimulated TNF-alpha 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-alpha production and weight loss will require further understanding of the relationship between energy metabolism and TNF-alpha production in these patients.
de Godoy
I
I
Department of Medicine, University of Pittsburgh Medical Center, Pennsylvania, USA.
Donahoe
M
M
Calhoun
W J
WJ
Mancino
J
J
Rogers
R M
RM
D000368:Aged; D002478:Cells, Cultured; D004734:Energy Metabolism; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008173:Lung Diseases, Obstructive / Q000097:blood* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014797:Vital Capacity; D015431:Weight Loss
D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha