Participation of Leukotriene D_4 and Tumor Necrosis Factor on Lipopolysaccharide-Induced Airway Hyperresponsiveness in Guinea Pigs

概要

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In guinea pigs, a marked increase in airway responsiveness to acetylcholine (Ach) was observed at 2h after lipopolysaccharide (LPS) inhalation. To examine the mediators responsible for the airway hyperresponsiveness, the changes of peptide-leukotrienes (LTs), tumor necrosis factor (TNF), interleukin-1 (IL-1), histamine and 5-hydroxytryptamine (5-HT) levels in bronchoalveolar lavage fluid (BALF) were measured. Airway responsiveness to Ach reached a peak 2h after LPS inhalation. The influx of neutrophil into BALF increased gradually and reached a peak 24h after LPS inhalation. After the inhalation of LPS, LTD_4 and TNF contents in BALF increased within the first 2h after LPS inhalation. However, other mediators were not detected or increased 6h after LPS inhalation. Aeroinhalation of LTD_4 and murine recombinant TNF-α caused airway hyperresponsiveness in guinea pigs. In addition, a LTD_4 antagonist, BAYx7195,and an inhibitor of TNF, pentoxifylline, inhibited the LPS-induced airway hyperresponsiveness. These results suggest that LTs and/or TNF play an important role in the onset of airway hyperresponsiveness in guinea pigs.
公益社団法人日本薬学会の論文
1997-04-15