RELATIVE PRODUCTION OF TUMOR-NECROSIS-FACTOR A AND INTERLEUKIN-10 IN ADULT-RESPIRATORY-DISTRESS-SYNDROME

Background - The adult respiratory distress syndrome (ARDS) may be reg arded as an example of an uncontrolled or excessive inflammatory respo nse in which tumour necrosis factor alpha (TNF-alpha) has been propose d to play a central role. Interleukin 10 (IL-10) has been identified a s an important regulator of this response. The potential role for IL-1 0 in this context was investigated by measuring the relative productio n 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 w ere 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 AR DS. Bronchoalveolar lavage and venepuncture were performed within 24 h ours 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, a nd alveolar macrophage supernatants by sandwich enzyme linked immunoab sorbent assays. Results - The median IL-10 concentrations in the plasm a and BAL fluid of patients with ARDS were significantly lower than th e concentrations detectable in the plasma (median difference - 17.5, 9 5% 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 alveola r macrophage supernatants and the BAL fluid of patients with ARDS comp ared with at risk patients, although this did not reach statistical si gnificance. No difference was observed in the plasma concentrations of TNF-alpha between the two groups. The ratios of TNF-alpha to IL-10 pr otein 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 productio n of IL-10 between the two groups. Conclusions - This study highlights the potential importance of the pro-inflammmatory versus the anti-inf lammatory imbalance in ARDS which may be reflected by the ratio of IL- 10 and TNF-alpha in the lung.