title: 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.
abstract: 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 less than 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 less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Surgery and Anesthesia, Children's Hospital, Geneva, Switzerland.
authors.forename: P M
authors.initials: PM
authors.lastname: Suter
authors.forename: S
authors.initials: S
authors.lastname: Suter
authors.forename: E
authors.initials: E
authors.lastname: Girardin
authors.forename: P
authors.initials: P
authors.lastname: Roux-Lombard
authors.forename: G E
authors.initials: GE
authors.lastname: Grau
authors.forename: J M
authors.initials: JM
authors.lastname: Dayer
mesh_terms: D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D006801:Humans; D007239:Infections / Q000150:complications; D016898:Interferon-alpha / Q000032:analysis*; D007375:Interleukin-1 / Q000032:analysis*; D019272:Leukocyte Elastase; D016676:Macrophages, Alveolar / Q000378:metabolism*; D009104:Multiple Trauma / Q000150:complications; D010196:Pancreatic Elastase / Q000032:analysis*; D012128:Respiratory Distress Syndrome / Q000453:epidemiology / Q000209:etiology / Q000378:metabolism*; D012307:Risk Factors; D012771:Shock, Hemorrhagic / Q000150:complications; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis* / Q000037:antagonists & inhibitors
chemical_list: D016898:Interferon-alpha; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase