HIGH BRONCHOALVEOLAR LEVELS OF TUMOR-NECROSIS-FACTOR AND ITS INHIBITORS, INTERLEUKIN-1, INTERFERON, AND ELASTASE, IN PATIENTS WITH ADULT RESPIRATORY-DISTRESS SYNDROME AFTER TRAUMA, SHOCK, OR SEPSIS

Intrapulmonary activation of leukocytes and release of cellular mediators and enzymes are involved in the pathophysiology of the adult respiratory distress syndrome (ARDS). To investigate a possible role of local cytokines, we measured bronchoalveolar fluid (BALF) and plasma levels of tumor necrosis factor-alpha (TNF-alpha) and its soluble inhibitors (sTNF-RI + RII), interleukin-1-beta (IL-1-beta), Interferon-alpha (IFN-alpha), and granulocyte elastase in 14 patients at risk for ARDS and in 35 patients developing ARDS after trauma, sepsis, or shock. During clinical development of severe ARDS, BALF cytokines increased markedly: TNF-alpha from 116 +/- 36 to 10,731 +/- 5,048 pg/ml (mean +/- SEM), p = 0.001; sTNF-RI + RII from 3.7 +/- 1.4 to 24.6 +/- 2.6 ng/ml, p < 0.05; and IL-1-beta from 7,746 +/- 5,551 to 42,255 +/- 19,176 pg/ml, p = 0.01. Plasma cytokines were not increased in most patients, nor were they correlated with the development or severity of ARDS. BALF elastase was higher in patients developing ARDS than in those at risk but not going into pulmonary failure (0.97 +/- 0.26 versus 0.28 +/- 0.13 U/ml, p = 0.026), and the highest values were observed in the early stages of severe ARDS (1.85 +/- 0.39 U/ml). BALF elastase levels correlated with IFN-alpha (r = 0.72, p < 0.001). In conclusion, local release of TNF-alpha and IL-1-beta, possibly by pulmonary macrophages or other cells, and/or accumulation in the lung is associated with the development of ARDS. TNF-alpha recovered in BALF was found biologically inactive; this may be due to the presence of substantial amounts of its inhibitors. Increased IFN-alpha and elastase in BALF probably reflect intrapulmonary granulocyte activation and degranulation.