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Therefore, we investigated airway reactivity (AR) in response to methacholine (MCh) in IL-10 knockout (<jats:sup>\u2212\/\u2212<\/jats:sup>) mice compared with wild-type C57BL\/6 (C57) mice, in which airway NO production was measured as exhaled NO (E<jats:sub>NO<\/jats:sub>), and NO production was altered with administration of either NO synthase (NOS)-specific inhibitors or recombinant murine (rm)IL-10. AR, measured as enhanced pause in vivo, and tracheal ring tension in vitro were lower in IL-10<jats:sup>\u2212\/\u2212<\/jats:sup>mice by 25\u201350%, which was associated with elevated E<jats:sub>NO<\/jats:sub>levels (13 vs. 7 ppb). Administration of NOS inhibitors N<jats:sup>G<\/jats:sup>-nitro-l-arginine methyl ester (8 mg\/kg ip) or l- N<jats:sup>6<\/jats:sup>-(1-iminoethyl)-lysine (3 mg\/kg ip) to IL-10<jats:sup>\u2212\/\u2212<\/jats:sup>mice decreased E<jats:sub>NO<\/jats:sub>by an average of 50%, which was associated with increased AR, to levels similar to C57 mice. E<jats:sub>NO<\/jats:sub>in IL-10<jats:sup>\u2212\/\u2212<\/jats:sup>mice decreased in a dose-dependent fashion in response to administered rmIL-10, to levels similar to C57 mice (7 ppb), which was associated with a 30% increment in AR. Thus increased NO production in the absence of IL-10, decreased AR, which was reversed with inhibition of NO, either by inhibition of NOS, or with reconstitution of IL-10. These findings suggest that airway NO production can modulate airway smooth muscle contractility, resulting in airway hyporesponsiveness when IL-10 is absent.<\/jats:p>","DOI":"10.1152\/ajplung.00207.2004","type":"journal-article","created":{"date-parts":[[2004,12,24]],"date-time":"2004-12-24T02:33:11Z","timestamp":1103855591000},"page":"L868-L873","source":"Crossref","is-referenced-by-count":5,"title":["Enhanced nitric oxide production associated with airway hyporesponsiveness in the absence of IL-10"],"prefix":"10.1152","volume":"288","author":[{"given":"Bill T.","family":"Ameredes","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jigme M.","family":"Sethi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"He-Liang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Augustine M. 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