Pulmonary function changes and immunomodulation of cytokine expression by zafirlukast after sensitization and allergen challenge in brown Norway rats

• Published in: Clinical and experimental allergy Vol. 32; no. 6; pp. 960 - 966
• Main Authors: Lin, C.-C., Lin, C.-Y., Liaw, S.-F., Chen, A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.06.2002; Blackwell; Wiley Subscription Services, Inc
• Subjects: Adjuvants, Immunologic - biosynthesis; Animals; Anti-Asthmatic Agents - therapeutic use; Biological and medical sciences; bronchial asthma; bronchial hyper-reactivity; Bronchial Provocation Tests; Bronchoalveolar Lavage Fluid - chemistry; Bronchoalveolar Lavage Fluid - cytology; brown Norway rats; Cytokines - biosynthesis; Cytokines - drug effects; Cytokines - metabolism; Histamine and antagonists. Allergy; Immunization; Leukocytes - metabolism; Lung - drug effects; Lung - pathology; Lung - physiology; Male; maximal forced expiratory manoeuvre; Maximal Midexpiratory Flow Rate - drug effects; Maximal Midexpiratory Flow Rate - physiology; Medical sciences; Models, Animal; ovalbumin; Pharmacology. Drug treatments; Rats - immunology; Respiratory Function Tests; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Time Factors; Tosyl Compounds - therapeutic use; Total Lung Capacity - drug effects; Total Lung Capacity - physiology; zafirlukast; Allergy; Animal model; Spirometry; Hyperreactivity; Rat; Leukotriene D4; Antiasthma agent; Leukotriene C4; Obstructive pulmonary disease; Antagonist; Reverse transcription polymerase chain reaction; Biological receptor; Immunopathology; Respiratory disease; Arachidonic acid derivatives; Zafirlukast; Rodentia; Leukotriene E4; Asthma; Vertebrata; Chemotherapy; Mammalia; Treatment; Animal; Molecular biology
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1046/j.1365-2222.2002.01381.x

Summary Background The cysteinyl leukotrienes are known important mediators in bronchial asthma. Objective Our purpose was to evaluate the effect of zafirlukast on the late‐phase reaction, bronchial hyper‐responsiveness (BHR) and T cell‐related cytokine mRNA expression in ovalbumin (OA)‐sensitized brown Norway rats (BNRs). Methods Thirty BNRs were equally divided into three groups. Group I and II animals were sensitized and then provoked with OA. Zafirlukast was given intraperitoneally (i.p.) to group I  animals prior to provocation. Group II animals received i.p. normal saline. Group III animals (controls) were not sensitized and breathed aerosolized saline. After OA provocation, the animals were anaesthetized. Pulmonary function tests (PFT) were performed at baseline and after varying doses of acetylcholine. Thereafter, bronchoalveolar lavage (BAL) was performed and the lungs were examined histologically. Total RNA was extracted from lung tissue and reverse transcriptase‐polymerase chain reaction (RT‐PCR) was performed using primers for IL‐2, IL‐4, IL‐5, IL‐6, IL‐10, TNF‐α, IFN‐γ, iNOS and β‐actin. Results Group II OA‐treated BNRs had worse PFT results, more severe bronchoconstriction in response to acetylcholine, and more severe inflammation in lung tissue than the other two groups. Group II had higher IL‐2, IL‐4, IL‐10 and IFN‐γ cytokine levels in BAL fluid and higher IL‐2, IL‐4, IL‐5, IL‐6, IL‐10, IFN‐γ, TNF‐α and iNOS mRNA levels when compared with group I. Conclusion Zafirlukast is effective in preventing late‐phase bronchoconstriction and BHR, reducing inflammatory response, and decreasing IL‐2, IL‐4, IL‐5, IL‐6, IL‐10 and IFN‐γ and iNOS mRNA expression.