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Laboratory and Animal Investigations |

Neurokinin-1 and Neurokinin-2 Antagonism Inhibits Long-term Acid Fog-Induced Airway Hyperresponsiveness*

Shin Teramoto, MD; Hiroshi Tanaka, MD; Satoshi Kaneko, MD; Shosaku Abe, MD
Author and Funding Information

*From the Third Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.

Correspondence to: Shin Teramoto, MD, Third Department of Internal Medicine, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan; e-mail: teramoto@sapmed.ac.jp



Chest. 2003;123(2):524-529. doi:10.1378/chest.123.2.524
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Background: We recently reported that airway hyperresponsiveness (AHR) induced by a 6-h exposure to sulfuric acid (H2SO4) was inhibited by either the neurokinin (NK)-1 receptor antagonist, FK888, or the NK-2 receptor antagonist, SR48968, when administered immediately before the exposure. The aims of this study were to determine whether these antagonists have any therapeutic efficiency against AHR after long-term H2SO4 inhalation and to elucidate the mechanisms in ovalbumin sensitized guinea pigs.

Methods: Specific airway resistance (sRaw), AHR, and BAL fluid were analyzed after an 8-week exposure to H2SO4 aerosol (82 mg/m3, pH 1.7, 40 mOsm) or hypotonic saline solution (pH 5.9, 40 mOsm) as a control. The H2SO4 group then received a 2-week treatment with FK888, SR48968, or vehicle.

Results: The AHR and the eosinophil count in BAL fluid were significantly increased in the H2SO4 group compared to control animals, while sRaw was significantly elevated in both groups after the 8-week exposure. Treatment with both FK888 and SR48968 significantly reduced the AHR and tended to inhibit eosinophilia in BAL fluid, but sRaw did not change. The degree of AHR improvement with SR48968 was much larger than with FK888.

Conclusion: Our results show that both NK-1 and NK-2 receptor antagonists inhibited long-term H2SO4-induced AHR in sensitized guinea pigs, and the effect was much greater with an NK-2 antagonist. We suggest that NK-1 or NK-2 antagonism might partially inhibit the H2SO4-induced influx of eosinophils into the lung.

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