Effects of tranilast and pentoxifylline in a mouse model of chronic asthma using house dust mite antigen.
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.
Kim
Seung Joon
SJ
Division of Pulmonology, Department of Internal Medicine, College of Medicine, the Catholic University of Korea, Seoul 137-040, Korea.
Kim
Jin Woo
JW
Kim
Yong Hyun
YH
Lee
Sang Haak
SH
Yoon
Hyoung Kyu
HK
Kim
Chi Hong
CH
Ahn
Joong Hyun
JH
Lee
Jung Mi
JM
Kim
Jin Sook
JS
Kim
Seok Chan
SC
Lee
Sook Young
SY
Kwon
Soon Seog
SS
Kim
Young Kyoon
YK
D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D039741:Antigens, Dermatophagoides / Q000008:administration & dosage / Q000276:immunology*; D001249:Asthma / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology / Q000517:prevention & control; D055745:Bronchioles / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D002452:Cell Count; D004359:Drug Therapy, Combination; D004804:Eosinophils / Q000166:cytology; D005260:Female; D024022:Fibrillar Collagens / Q000378:metabolism; D020397:Goblet Cells / Q000473:pathology; D006965:Hyperplasia / Q000473:pathology / Q000517:prevention & control; D007073:Immunoglobulin E / Q000032:analysis / Q000097:blood / Q000276:immunology; D018793:Interleukin-13 / Q000032:analysis / Q000097:blood; D007962:Leukocytes / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D009130:Muscle, Smooth / Q000473:pathology; D010431:Pentoxifylline / Q000008:administration & dosage / Q000627:therapeutic use*; D011658:Pulmonary Fibrosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D013047:Specific Pathogen-Free Organisms; D053773:Transforming Growth Factor beta1 / Q000032:analysis / Q000097:blood; D062367:ortho-Aminobenzoates / Q000008:administration & dosage / Q000627:therapeutic use*
D018926:Anti-Allergic Agents; D039741:Antigens, Dermatophagoides; D024022:Fibrillar Collagens; D018793:Interleukin-13; D053773:Transforming Growth Factor beta1; D062367:ortho-Aminobenzoates; D007073:Immunoglobulin E; C012293:tranilast; D010431:Pentoxifylline