Pulmonary function changes and immunomodulation of Th 2 cytokine expression induced by aminophylline after sensitization and allergen challenge in brown Norway rats

Lin, Ching-Chi MD
Lin, Ching-Yuang MD, PhD
Liaw, Shwu-Fang MB
Chen, Ann MD

^*Chest Division and Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan.
^†Department of Pediatrics, Veterans General Hospital, Taipei, Taiwan.
^‡Department of Pathology, Tri-service General Hospital, Taipei, Taiwan.

Requests for reprints should be addressed to: Dr. Ching-Chi Lin Chest Division, Department of Internal Medicine Mackay Memorial Hospital, 92, Sec 2 Chung Shan North Road Taipei, Taiwan. E-mail:[email protected]

The research was partially supported by NSC 88-2314-B-195-009-M50.

Received for publication November 30, 2000.

Accepted for publication in revised form October 15, 2001.

Annals of Allergy, Asthma, & Immunology 88(2):p 215-222, February 2002.

Background and 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-γ, inducible nitric oxide synthase, and β-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-α and inducible nitric oxide synthase mRNA expression than the other three groups. Expression of IL-2 and interferon-γ 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.

Ann Allergy Asthma Immunol 2002;88:215-222.