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| Item Type: | Article |
|---|---|
| Title: | Pathophysiologic quantities of endotoxin-induced tumor necrosis factor-alpha release in whole blood from patients with chronic heart failure |
| Creators Name: | Genth-Zotz, S. and von Haehling, S. and Bolger, A. and Kalra, P.R. and Wensel, R. and Coats, A.J.S. and Anker, S.D. |
| Abstract: | Bacterial endotoxin activity is elevated in patients with decompensated chronic heart failure (HF) and acts as a potent stimulus for immune activation. We sought to determine whether endotoxin, at an activity level seen in vivo (around 0.6 EU/ml), is sufficient to stimulate the secretion of tumor necrosis factor-α (TNF-α) and TNF-α soluble receptor (sTNFR2) in ex vivo whole blood from patients with HF. We studied 15 patients with HF (aged 65 ± 1.9 years, New York Heart Association class 2.1 ± 0.3, left ventricular ejection fraction 31 ± 5%; mean ± SEM), of whom 5 had cardiac cachexia, and 7 healthy control subjects (59 ± 5 years, p = NS). Reference endotoxin was added to venous blood at concentrations of 0.6, 1.0, and 3.0 EU/ml, and was incubated for 6 hours. Endotoxin induced a dose-dependent increase in TNF-α release (p <0.05 in all groups). Patients with noncachectic HF produced significantly more TNF-α compared with controls after stimulation with 0.6, 1.0, and 3.0 EU/ml of endotoxin (113 ± 46 vs 22 ± 4 [p = 0.009], 149 ± 48 vs 34 ± 4 [p = 0.002], and 328 ± 88 vs 89 ± 16 pg/ml [p = 0.002], respectively; mean ± SEM). Patients with cardiac cachexia produced significantly less TNF-α compared with patients without cardiac cachexia for all given concentrations (all p <0.05, analysis of variance p = 0.02). Production of sTNFR2 was greater at all concentrations of endotoxin versus controls (all p <0.05, analysis of variance p = 0.002). Plasma endotoxin levels were higher in patients with cardiac cachexia (4.3 times higher than in control subjects, p <0.005). Thus, low endotoxin activity, at levels seen in vivo in patients with HF, induces significant TNF-α and sTNFR2 production ex vivo. These results suggest that elevated plasma endotoxin activity observed in patients with HF is of pathophysiologic relevance. |
| Keywords: | Cachexia, Congestive Heart Failure, Endotoxins, Enzyme-Linked Immunosorbent Assay, Tumor Necrosis Factor-{alpha}, Tumor Necrosis Factor Receptors |
| Source: | American Journal of Cardiology |
| ISSN: | 0002-9149 |
| Publisher: | Elsevier |
| Volume: | 90 |
| Number: | 11 |
| Page Range: | 1226-1230 |
| Date: | 1 December 2002 |
| Official Publication: | https://doi.org/10.1016/S0002-9149(02)02839-4 |
| PubMed: | View item in PubMed |
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