Immunoparalysis in patients with severe trauma and the effect of inhaled interferon-gamma.
OBJECTIVE
To evaluate the local immune status in patients with severe trauma and the influence of interferon-gamma on patients with immunoparalysis.


METHODS
Fifty-two mechanically ventilated patients with severe multiple trauma.


METHODS
A 14-bed polyvalent intensive care unit.


METHODS
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.


METHODS
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.
Intensive Care Unit, Ioannina University Hospital, Ioannina, Greece. gnakos@cc.uoi.gr
George
G
Nakos
Vasiliki D
VD
Malamou-Mitsi
Alexandra
A
Lachana
Aikaterini
A
Karassavoglou
Eirini
E
Kitsiouli
Niki
N
Agnandi
Marilena E
ME
Lekka
D000280:Administration, Inhalation; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000209:etiology* / Q000517:prevention & control*; D015601:Injury Severity Score; D007371:Interferon-gamma / Q000008:administration & dosage*; D008875:Middle Aged; D012121:Respiration, Artificial; D014947:Wounds and Injuries / Q000150:complications* / Q000276:immunology*
D000998:Antiviral Agents; D006684:HLA-DR Antigens; D007371:Interferon-gamma