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

Abstract

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 microg 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 A2, interleukin-1beta, 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 1a from 17 +/- 5% to 46 +/- 9%. In parallel, platelet-aggregating factor and interleukin-1beta as well as the specific activities of phospholipase A2 and platelet-aggregating factor acetylhydrolase significantly increased. In contrast, interleukin-10 decreased after interferon-gamma therapy. In group 1b, 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 1a than in group 1b. 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.