Immunoparalysis in patients with severe trauma and the effect of inhaled interferon-γ

Objective: To evaluate the local immune status in patients with severe trauma and the influence of interferon-gamma on patients with immunoparalysis. Patients: Fifty-two mechanically ventilated patients with severe multiple trauma. Setting: A 14-bed polyvalent intensive care unit. Interventions: The local immune status was evaluated by examining bronchoalveolar lavage fluid. Subsequently, the patients were divided into two groups: immunoparalyzed (group 1) and nonimmunoparalyzed (group 2). Immunoparalysis was defined as a decreased level of human leukocyte antigen-DR expression of alveolar macrophages in <30%. Patients with immunoparalysis were treated with 100 Kg of inhaled recombinant human interferon-gamma, three times daily (group 1a, 11 patients) or placebo (group 1b, ten patients). A second bronchoalveolar lavage fluid was obtained 3 days after the initiation of therapy. Measurements: The alterations in human leukocyte antigen-DR expression, as well as in pro- and anti-inflammatory markers, such as platelet-aggregating factor, phospholipase A(2), interleukin-1beta, 0, platelet-aggregating factor acetylhydrolase, and interleukin-10, were evaluated in the bronchoalveolar lavage fluids. Results: In 21 of 52 (40%) patients, immunoparalysis was established. After interferon-gamma administration, the level of human leukocyte antigen-DR expression increased in group 1 a from 17 +/- 5% to 46 +/- 9%. In parallel, platelet-aggregating factor and interleukin-1beta as well as the specific activities of phospholipase A(2) and platelet-aggregating factor acetylhydrolase significantly increased. In contrast, interleukin-10 decreased after interferon-gamma therapy. In group 1 b, no statistically significant changes appeared in the levels of human leukocyte antigen-DR expression or in the concentrations of inflammatory mediators. The incidence of ventilator-associated pneumonia was significantly lower in group la than in group 1 b. The administration of interferon-gamma did not affect the outcome of the patients. Conclusions: A significant proportion of multiply injured patients developed immunoparalysis. The administration of interferon-gamma resulted in the recovery of levels of human leukocyte antigen-DR expression in alveolar macrophages, influenced the inflammatory reaction, and decreased the incidence ventilator-associated pneumonia, without affecting the patients' outcome.