s-145 and Pneumonia

We examined both a possible association of bronchial hyperresponsiveness with lung inflammatory responses and the role of thromboxane (Tx) A2 in these responses after lipopolysaccharide (LPS) exposure in guinea pigs treated with metyrapone, a cortisol synthesis inhibitor. The increase in bronchial responsiveness to i.v. acetylcholine was transient, with a peak at 2 h after LPS exposure, which was associated with increases in TxB2 and tumor necrosis factor in bronchoalveolar lavage (BAL) fluid. However, the levels of 6-keto-prostaglandin (PG) F1 alpha, interleukin-1 and interleukin-6 in BAL fluid, and the influx of leukocytes in airway and pulmonary edema were not associated with bronchial hyperresponsiveness. Oral administration of S-1452, a selective TxA2 receptor antagonist, markedly suppressed bronchial hyperresponsiveness without affecting cellular responses, pulmonary edema and production of PGs and cytokines. These findings suggest that LPS-induced bronchial hyperresponsiveness is dependent on secondarily generated TxA2, which appears to be independent of lung inflammation.

Topics: Animals; Bridged Bicyclo Compounds; Bronchial Hyperreactivity; Cytokines; Fatty Acids, Monounsaturated; Guinea Pigs; Interleukin-1; Interleukin-6; Leukocytes; Lipopolysaccharides; Metyrapone; Pneumonia; Prostaglandins; Pulmonary Edema; Receptors, Prostaglandin; Thromboxane A2; Tumor Necrosis Factor-alpha