Inhaled IL-10 reduces biotrauma and mortality in a model of ventilator-induced lung injury

Background: High-pressure ventilation induces barotrauma and pulmonary inflammation, thus leading to ventilator-induced lung injury (VILI). By limiting the pulmonal. inflammation cascade the anti-inflammatory cytokine interleukin (IL)-10 may have protective effects. Via inhalation, IL-10 reaches the pulmonary system directly and in high concentrations. Methods: Thirty six mate, anesthetized and mechanically ventilated Sprague-Dawley rats were randomly assigned to the following groups (n = 9, each): SHAM: pressure controlled ventilation with p(max) = 20 cmH(2)O, PEEP = 4; VILI: ventilator settings were changed for 20 min to p(max) = 45 cmH(2)O, PEEP = 0; IL-10(high): inhalation of 10 mu g/kg IL-10 prior to induction of VILI; and IL-10(low): inhalation of 1 mu g/kg IL-10 prior to induction of VILI. All groups were ventilated and observed for 4 h. Results: High-pressure ventilation increased the concentrations of macrophage inflammatory protein (MIP)-2 and IL-1 beta in bronchoalveolar lavage fluid (BALF) and plasma. This effect was reduced by the inhalation of IL-10 (10 mu g/kg). Additionally, IL-10 increased the animal survival time (78% vs. 22% 4-h mortality rate) and reduced NO-release from ex vivo cultured alveolar macrophages. Moreover, VILI-induced pulmonary heat shock protein-70 expression was reduced by IL-10 aerosol in a dose-dependent manner. Similarly, the activation of matrix metalloproteinase (MMP)-9 in BALF was reduced dose-dependently by IL-10. IL-10-treated animals showed a tower macroscopic lung injury score and less impairment of lung integrity and gas exchange. Conclusions: Prophylactic inhalation of IL-10 improved survival and reduced lung injury in experimental VILI. Results indicate that this effect maybe mediated by the inhibition of stress-induced inflammation and pulmonary biotrauma. (C) 2008 Elsevier Ltd. All rights reserved.