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This Article Full Text Full Text (PDF) All Versions of this Article: 286/1/L98    most recent 00053.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Deleuze, V. Articles by Vargaftig, B. B. Search for Related Content PubMed PubMed Citation Articles by Deleuze, V. Articles by Vargaftig, B. B.

LPS-induced bronchial hyperreactivity: interference by mIL-10 differs according to site of delivery

¹Unité Mixte de Recherche 7001 Centre National de la Recherche Scientifique/Ecole Nationale de Chimie de Paris/Aventis Pharma—Gencell Société Anonyme, 94403 Vitry-sur-Seine Cedex, and ²Unité de Pharmacologie Cellulaire—Institut Pasteur, 75015 Paris, France

Submitted 25 February 2003 ; accepted in final form 9 September 2003

When administered to mice systemically or via the airways, LPS induces bronchoconstriction (BC) and/or bronchopulmonary hyperreactivity (BHR), associated with inflammation. Accordingly, a relationship between inflammation and allergic and nonallergic BHR can be hypothesized. We therefore studied the interference of the anti-inflammatory cytokine murine IL-10 (mIL-10) with LPS-induced lung inflammation, BC, and BHR. mIL-10 was administered directly into the airways by intranasal instillation or generated in vivo after muscle electrotransfer of mIL-10-encoding plasmid. Electrotransfer led to high mIL-10 circulating levels for a longer time than after the injection of recombinant mIL-10 (rmIL-10). rmIL-10 administered intranasally reduced lung inflammation and BHR after LPS administration into airways. It also reduced the ex vivo production of TNF- by LPS-stimulated lung tissue explants. Two days after electrotransfer, mIL-10 blood levels were elevated, but lung inflammation, BC, and BHR persisted unaffected. Blood mIL-10 reaches the airways poorly, which probably accounts for the ineffectiveness of mIL-10-encoding plasmid electrotransfer. When LPS was aerosolized 15 days after electrotransfer, lung inflammation persisted but BHR was significantly reduced, an effect that may be related to the longer exposure of the relevant cells to mIL-10. The dissociation between inflammation and BHR indicates that both are not directly correlated. In conclusion, this study shows that mIL-10 is efficient against BHR when present in the airway compartment. Despite this, the muscle electrotransfer with mIL-10-encoding plasmid showed a protective effect against BHR after a delay of 2 wk that should be further investigated.

murine interleukin-10; gene transfer; gene therapy; electroporation; lipopolysaccharide; lung inflammation