Interleukin-10 aerosol reduces proinflammatory mediators in bronchoalveolar fluid of endotoxemic rat

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Objective We aimed to clarify if inhaled interleukin (IL)-10 attenuates pulmonary and systemic inflammation as indicated by reduced content of proinflammatory mediators in bronchoalveolar lavage fluid (BALF) and plasma in experimental endotoxemia in the rat. Design Laboratory experiment. Setting University research institute. Subjects Anesthetized, ventilated rats (sd, 550 +/- 50 g). Interventions Rats were randomly treated as follows: Nebulized IL-10 (calculated deposition fraction, 0.1 microg/lung) was administered in eight rats before infusion of lipopolysaccharide (5 mg/kg, intravenously). Eight animals received the same insult with no further treatment. Eight rats served as controls without endotoxemia but with aerosolized saline. Measurements and main results BALF and plasma levels of tumor necrosis factor (TNF)-alpha, IL-1beta, IL-6, interferon (IFN)-gamma, and RANTES were analyzed. Alveolar macrophages were cultured ex vivo for nitrite assay. In those animals treated with IL-10-aerosol, BALF levels of proinflammatory cytokines were reduced significantly compared with animals without IL-10 therapy (TNF-alpha, -87%; IL-1beta, -73%; IL-6, -44%; IFN-gamma, -39%; RANTES, -84%). In addition, nitrite release from cultured alveolar macrophages was suppressed by IL-10 inhalation (-96%). With the exception of TNF-alpha, similar results were observed for plasma levels of proinflammatory cytokines. Conclusions The present data indicate that nebulized IL-10 reached the lungs in therapeutic effective concentrations and elicited anti-inflammatory effects on immunocompetent cells that are comparable to those already known from its intravenous administration in experimental endotoxemia.