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Title: [The evolvement of Th1/Th2 imbalance in the process of airway inflammation in a rat asthmatic model].
Author: Shi JH, Li TS, Lin YG.
Journal: Zhonghua Jie He He Hu Xi Za Zhi; 2004 Aug; 27(8):519-23. PubMed ID: 15387999.
Abstract:
OBJECTIVE: T lymphocytes play an important role in the development of asthmatic airway inflammation. By observing the production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) released by peripheral T lymphocytes in asthmatic rat models, this study was designed to clarify the changes of T lymphocytes during the course of airway inflammation. The influence of dexamethasone pre-treatment on the production of IFN-gamma and IL-4 by T lymphocytes was also investigated in the study. METHODS: Twenty-four rats were divided into the study group (group A) and the control group (group B). In the study group, rats were subdivided into two groups with 8 rats in each group. one group (group A(2)) received pre-treatment with intraperitoneal injection with dexamethasone (10 mg/kg), and another group (group A(1)) did not receive dexamethasone pre-treatment, The control group was matched with the study group with regard to both age and weight. Rats were sensitized and challenged by ovalbumin (OVA), and blood samples were obtained and the percentage of IFN-gamma(+)CD(4)(+), IFN-gamma(+)CD(8)(+) and IL-4(+)CD(4)(+) cells were assessed by intracellular cytokine staining and flow cytometric analysis at 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, 24 h, 36 h, 48 h, 72 h, 6 d, 9 d, 12 d, and 15 d after OVA challenge. RESULTS: In group A(1), the peripheral IFN-gamma(+)CD(4)(+) cells, IFN-gamma(+)CD(8)(+) cells, and IL-4 CD(4)(+) cells increased 2 h after OVA challenge [(5.7 +/- 1.6)%, [(11.5 +/- 5.1)%, (1.66 +/- 0.95)%] compared with group A(2) [(2. 6 +/- 1.3)%, (6.1 +/- 1.8)%, (0.77 +/- 0.37)%, P < 0.05 respectively] and group B [(1.8 +/- 0.7)%, (3.9 +/- 1.5)%, (0.65 +/- 0.12)%, P < 0.05 respectively]. The peripheral IFN-gamma(+)CD(4)(+) cells and IFN-gamma(+) CD(8)(+) cells in group A(1) reached their maximal level at 10 h [(9.9 +/- 4.4)%, (38.7 +/- 6.3)%] compared with group A(2) [(4.9 +/- 1.7)%, (15.7 +/- 8.7)%, P < 0.05 respectively and group B [(1.5 +/- 0.5)%, (6.4 +/- 1.5)%, P < 0.05 respectively], and then decreased afterward. The IL-4(+) CD(4)(+) cells in group A(1) at 10 h after challenge was (2.16 +/- 0.75)%. There was no statistical difference compared with group A(2) [(1.39 +/- 0.77)%, P > 0.05], but it was higher than group B [(0.68 +/- 0.15)%, P < 0.05]. The highest level of IL-4(+) CD(4)(+) cells of group A(1) was observed at 36 h [(4.0 +/- 1.6)%], and there was a statistical difference compared with group A(2) [(1.5 +/- 1.0)%, P < 0.05] and group B [(0.7 +/- 0.3)%, P < 0.05]. CONCLUSIONS: Both IFN-gamma and IL-4 generated by peripheral blood T cells in the rat asthmatic models played a role in the development of airway inflammation. INF-gamma dominated at early stage of the airway inflammation, whereas IL-4 took the major effect at the late stage of inflammation. The production of IFN-gamma and IL-4 by T lymphocytes in the asthmatic model was inhibited significantly by dexamethasone.

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