tranilast and Bronchial-Hyperreactivity

Tranilast has been used in allergic diseases because of its inhibitory effect on mast cells; it also has an anti-fibrotic effect in several diseases. Pentoxifylline (PTX), a methylxanthine derivative, is a potent anti-inflammatory drug that is known to manifest its effect through the inhibition of Th1 cytokine, but with an uncertain effect on Th2 cytokine. Seven-week-old female BALB/c mice were studied as a chronic asthma model. The mice were challenged with house dust mite (HDM) antigen for 7 weeks. Each group of mice was given an intraperitoneal injection of tranilast, PTX, or tranilast plus PTX before antigen administration. In this mouse model of chronic asthma, tranilast, and PTX each had an inhibitory effect on airway remodeling as well as on airway hyperresponsiveness (AHR) and airway inflammation. The improved events of these drugs were related with the inhibition of the Th2 cytokine IL-13 and TGF-beta 1. Immunohistochemical analysis showed that decreases in the peribronchial trichrome stained area in each treatment group were associated with improvements in the peribronchial smooth muscle hyperplasia, collagen type I, and collagen type III deposition. These drugs could have potential beneficial effects on chronic asthma, especially with respect to airway remodeling.

Topics: Animals; Anti-Allergic Agents; Antigens, Dermatophagoides; Asthma; Bronchial Hyperreactivity; Bronchioles; Bronchoalveolar Lavage Fluid; Cell Count; Drug Therapy, Combination; Eosinophils; Female; Fibrillar Collagens; Goblet Cells; Hyperplasia; Immunoglobulin E; Interleukin-13; Leukocytes; Mice; Mice, Inbred BALB C; Muscle, Smooth; ortho-Aminobenzoates; Pentoxifylline; Pulmonary Fibrosis; Specific Pathogen-Free Organisms; Transforming Growth Factor beta1

To determine whether tazanolast inhibits airway hyperresponsiveness, we studied the effect of this drug on platelet activating factor (PAF)-induced airway hyperresponsiveness in guinea pigs. Inhalation of PAF (1 microgram/ml) caused significant airway hyperresponsiveness to acetylcholine (p < 0.01) or histamine (p < 0.05). Pretreatment with tazanolast (30-300 mg/kg) produced a dose-dependent inhibition of airway hyperresponsiveness induced by PAF inhalation, and significant inhibition (p < 0.05) was obtained with the drug (300 mg/kg). Aspirin also inhibited PAF-induced airway hyperresponsiveness, while tranilast produced hardly any inhibition. From these results, it is suggested that tazanolast is effective in inhibiting airway hyperresponsiveness.

Topics: Animals; Aspirin; Bronchial Hyperreactivity; Guinea Pigs; Histamine Antagonists; Male; ortho-Aminobenzoates; Platelet Activating Factor; Tetrazoles