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

Authors: Hofstetter, C  Flondor, M  Hoegl, S  Muhl, H  Zwissler, B 
Citation: Hofstetter C, etal., Crit Care Med. 2005 Oct;33(10):2317-22.
Pubmed: (View Article at PubMed) PMID:16215387

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.


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RGD Object Information
RGD ID: 2307171
Created: 2009-05-20
Species: All species
Last Modified: 2009-05-20
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.