Effect of azelastine on endotoxin-induced airway hyperresponsiveness in mice.
We examined the role of lipopolysaccharide (LPS) on the pulmonary inflammatory process in mice, including the release of interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) by macrophages, and investigated the mechanism of action of azelastine (AZ) on the release of these two cytokines. Intratracheal instillation of 1.0 microgram/ml LPS into BALB/c mice caused a significant increase in both IL-1 beta and TNF-alpha in aqueous lung extracts. These changes were modified, under control conditions, by a single dose of 0.05 mg/kg of AZ administered 1 and 11 h after LPS infusion. Intratracheal instillation of LPS also caused a significant increase in bronchial hyperresponsiveness to methacholine (Mch). AZ significantly inhibited Mch responsiveness in LPS-infused mice compared with nontreated control mice. Our results suggested that intratracheal instillation of LPS induces the secretion of macrophage cytokines in the airways of mice, accounting, at least partly, for LPS-induced airway hyperresponsiveness. Our results also indicate that the attenuating effect of AZ on LPS-induced airway hyperresponsiveness could be explained by its inhibitory effect on macrophage cytokine production.
Konno
S
S
First Department of Internal Medicine, School of Medicine, Showa University, Tokyo, Japan.
Asano
K
K
Gonokami
Y
Y
Kurokawa
M
M
Kawazu
K
K
Okamoto
K
K
Adachi
M
M
D000280:Administration, Inhalation; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007375:Interleukin-1 / Q000032:analysis; D008070:Lipopolysaccharides; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010793:Phthalazines / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D001993:Bronchodilator Agents; D007375:Interleukin-1; D008070:Lipopolysaccharides; D010793:Phthalazines; D014409:Tumor Necrosis Factor-alpha; C020976:azelastine