Participation of Leukotriene D₄ and Tumor Necrosis Factor on Lipopolysaccharide-Induced Airway Hyperresponsiveness in Guinea Pigs

抄録

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, LTD₄ 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 LTD₄ and murine recombinant TNF-α caused airway hyperresponsiveness in guinea pigs. In addition, a LTD₄ 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.