Relative production of tumour necrosis factor alpha and interleukin 10 in adult respiratory distress syndrome

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Abstract
BACKGROUND: The adult respiratory distress syndrome (ARDS) may be regarded as an example of an uncontrolled or excessive inflammatory response in which tumour necrosis factor alpha (TNF-alpha) has been proposed to play a central role. Interleukin 10 (IL-10) has been identified as an important regulator of this response. The potential role for IL-10 in this context was investigated by measuring the relative production of IL-10 and TNF-alpha protein in the plasma, bronchoalveolar lavage (BAL) fluid, and alveolar macrophage culture supernatants of patients with, or at risk of developing, ARDS. METHODS: Twenty six patients were studied from three groups at risk of or with ARDS: sepsis (n = 12), multiple trauma (n = 8), and perforated bowel (n = 6). Ten patients had ARDS. Bronchoalveolar lavage and venepuncture were performed within 24 hours of arrival on the intensive therapy unit or of diagnosis of ARDS. IL-10 and TNF-alpha protein were detected in the plasma, BAL fluid, and alveolar macrophage supernatants by sandwich enzyme linked immunoabsorbent assays. RESULTS: The median IL-10 concentrations in the plasma and BAL fluid of patients with ARDS were significantly lower than the concentrations detectable in the plasma (median difference-17.5, 95% CI -52.4 to 1.31, p < 0.05) and BAL fluid of at risk patients (median difference -32.1, 95% CI -47.5 to 2.3, p < 0.05). There was a tendency towards enhanced concentrations of TNF-alpha detectable in the alveolar macrophage supernatants and the BAL fluid of patients with ARDS compared with at risk patients, although this did not reach statistical significance. No difference was observed in the plasma concentrations of TNF-alpha between the two groups. The ratios of TNF-alpha to IL-10 protein in the BAL fluid of patients with ARDS and at risk patients were 3.52 and 0.85, respectively (median difference 1.44, 95% CI 0.07 to 5.01, p < 0.01). There was no difference in alveolar macrophage production of IL-10 between the two groups. CONCLUSIONS: This study highlights the potential importance of the pro-inflammatory versus the anti-inflammatory imbalance in ARDS which may be reflected by the ratio of IL-10 and TNF-alpha in the lung.

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