Participation of leukotriene D4 and tumor necrosis factor on lipopolysaccharide-induced airway hyperresponsiveness in guinea pigs.
In guinea pigs, a marked increase in airway responsiveness to acetylcholine (Ach) was observed at 2 h 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 2 h after LPS inhalation. The influx of neutrophil into BALF increased gradually and reached a peak 24 h after LPS inhalation. After the inhalation of LPS, LTD4 and TNF contents in BALF increased within the first 2 h after LPS inhalation. However, other mediators were not detected or increased 6 h after LPS inhalation. Aeroinhalation of LTD4 and murine recombinant TNF-alpha 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.
Uno
T
T
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Tanaka
H
H
Nakai
N
N
Nagai
H
H
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016084:Bronchoconstriction / Q000187:drug effects; D004926:Escherichia coli; D006168:Guinea Pigs; D006632:Histamine / Q000378:metabolism; D006880:Hydroxy Acids / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism; D017998:Leukotriene D4 / Q000378:metabolism* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D010431:Pentoxifylline / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
D006880:Hydroxy Acids; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D012701:Serotonin; D017998:Leukotriene D4; D006632:Histamine; D000109:Acetylcholine; D010431:Pentoxifylline; C092294:BAY x 7195