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


METHODS
Laboratory experiment.


METHODS
University research institute.


METHODS
Anesthetized, ventilated rats (sd, 550 +/- 50 g).


METHODS
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.


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.
Hofstetter
Christian
C
Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Johann Wolfgang Goethe-University of Frankfurt, Germany.
Flondor
Michael
M
Hoegl
Sandra
S
Muhl
Heiko
H
Zwissler
Bernhard
B
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D016207:Cytokines / Q000378:metabolism*; D019446:Endotoxemia / Q000139:chemically induced / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism*; D016753:Interleukin-10 / Q000008:administration & dosage / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008297:Male; D009330:Nebulizers and Vaporizers; D051381:Rats; D017207:Rats, Sprague-Dawley
D000336:Aerosols; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C482199:lipopolysaccharide, E coli O55-B5; D016753:Interleukin-10