Pulmonary function changes and immunomodulation of cytokine expression by zafirlukast after sensitization and allergen challenge in brown Norway rats.
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-alpha, IFN-gamma, iNOS and beta-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-gamma cytokine levels in BAL fluid and higher IL-2, IL-4, IL-5, IL-6, IL-10, IFN-gamma, TNF-alpha and iNOS mRNA levels when compared with group I.


CONCLUSIONS
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-gamma and iNOS mRNA expression.
Lin
C-C
CC
Chest Division and Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan. cclin@ms2.mmh.otg.tw
Lin
C-Y
CY
Liaw
S-F
SF
Chen
A
A
D000276:Adjuvants, Immunologic / Q000096:biosynthesis*; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects* / Q000378:metabolism; D007114:Immunization; D007211:Indoles; D007962:Leukocytes / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D008297:Male; D008450:Maximal Midexpiratory Flow Rate / Q000187:drug effects / Q000502:physiology; D023421:Models, Animal; D048448:Phenylcarbamates; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats / Q000276:immunology*; D012129:Respiratory Function Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides; D013997:Time Factors; D014105:Tosyl Compounds / Q000627:therapeutic use*; D014109:Total Lung Capacity / Q000187:drug effects / Q000502:physiology
D000276:Adjuvants, Immunologic; D018927:Anti-Asthmatic Agents; D016207:Cytokines; D007211:Indoles; D048448:Phenylcarbamates; D012333:RNA, Messenger; D013449:Sulfonamides; D014105:Tosyl Compounds; C062735:zafirlukast