Alveolar interleukin-10 regulates neutrophil apoptosis in severely traumatized patients

The lung produces a localized immunologic response to systemic trauma, characterized by an initial proinflammatory period with production of interleukin (IL)-8 and IL-18, followed by an anti-inflammatory phase with elevated levels of IL-10. Recent studies have shown a correlation between alveolar IL-10 and the rate of local neutrophil apoptosis. The aim of the present study was to further characterize the association of alveolar IL-8 and IL-10 after trauma with neutrophil activation, apoptosis, and phagocytic capacity.

Bronchoalveolar lavage fluid (BALF) was obtained from 17 trauma patients with an Injury Severity Score >/=16 who required mechanical ventilation. Neutrophils from venous blood of healthy volunteers were incubated in either (1) cell culture media (control), (2) culture media + BALF, (3) culture media + BALF + anti-IL-8 neutralizing antibody, or (4) culture media + BALF + anti-IL-10. Surface CD11b expression, ability to phagocytose fluorescent bacteria, and neutrophil apoptosis were determined by flow cytometry.

Phagocytosis and CD11b expression were both augmented on postinjury day 1 when compared with controls. Neutralization of IL-10 or IL-8 produced no significant differences in phagocytosis or CD11b expression. However, neutralization of IL-10 significantly decreased the rate of apoptosis in samples from postinjury day 1.

Phagocytosis and CD11b expression on neutrophils are IL-8 and IL-10 independent. However, our data indicate that alveolar neutrophil apoptosis is dependent on IL-10 at early time points after injury. Elucidation of this pathway may allow novel interventions to prevent posttraumatic pulmonary dysfunction.