Pulmonary function changes and immunomodulation of Th 2 cytokine expression induced by aminophylline after sensitization and allergen challenge in brown Norway rats.
OBJECTIVE
Evidence has shown that aminophylline has bronchoprotective, anti-inflammatory, and immunomodulatory effects. Our purpose was to evaluate the effect of different doses of aminophylline on the late-phase reaction, bronchial hyperresponsiveness (BHR) and T cell-related cytokine mRNA expression in brown Norway rats induced by ovalbumin (OA) sensitization.


METHODS
Forty rats were equally divided into four groups. Groups I, II, and III animals were sensitized and subsequently provoked with OA. Aminophylline 25 mg/kg was given intraperitoneally to the group I animals and 5 mg/kg to group II animals. Group III animals received intraperitoneal normal saline. Group IV breathed aerosolized saline as a control. After OA provocation, the animals were anesthetized. Pulmonary function tests were performed at baseline and after varying doses of acetylcholine. Thereafter, bronchoalveolar lavage was performed and the lungs were examined histologically. Total RNA was extracted from lung tissue and reverse transcriptase-polymerase chain reaction was performed using primers for interleukin (IL)-2, IL-4, IL-5, IL-6, IL-10, interferon-gamma, inducible nitric oxide synthase, and beta-actin.


RESULTS
Group III had worse pulmonary function tests, more severe BHR, and more severe lung inflammation, higher IL-4 and IL-10 cytokine levels in bronchoalveolar lavage fluid, and higher IL-4, IL-5, IL-6, IL-10, tumor necrosis factor-alpha and inducible nitric oxide synthase mRNA expression than the other three groups. Expression of IL-2 and interferon-gamma was significantly reduced in group III.


CONCLUSIONS
Both low and high dose aminophylline are effective in preventing late-phase bronchoconstriction, BHR, and an inflammatory response. Aminopylline decreases T helper cell 2-related cytokine mRNA expression but increases T helper cell 1-related cytokines mRNA expression.
Lin
Ching-Chi
CC
Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan. cclin@ms2.mmh.org.tw
Lin
Ching-Yuang
CY
Liaw
Shwu-Fang
SF
Chen
Ann
A
D000485:Allergens / Q000276:immunology; D000628:Aminophylline / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D010047:Ovalbumin / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012129:Respiratory Function Tests; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013806:Theophylline / Q000097:blood
D000485:Allergens; D016207:Cytokines; D012333:RNA, Messenger; D000628:Aminophylline; D010047:Ovalbumin; D013806:Theophylline