[The evolvement of Th1/Th2 imbalance accommodates to the progress of airway inflammation in asthmatic subjects and rat model].
OBJECTIVE
To observe the production of IFN-gamma and IL-4 released in peripheral T lymphocytes in asthmatic patients and rat models and to clarify the dynamic changes of proliferation and differentiation of T lymphocytes during the progress of airway inflammation.


METHODS
Twenty patients with moderate to severe acute exacerbation and 15 patients with remission of asthma were included in this study. Ten normal volunteers were also enrolled as control group. T lymphocytes were obtained from their peripheral blood and the percentage of IFN-gamma(+)CD4(++), IFN-gamma + CD8(++) and IL-4(+)CD4(++) cells were determined by flow cytometric method. Asthmatic rat models were established by sensitizing and challenging by ovalbumin (OVA), and the blood samples were taken and the percentage of IFN-gamma(+)CD4(+), IFN-gamma + CD8(+) and IL-4 + CD4(+) cells were assessed 2, 4, 6, 8, 10, 12, 24, 48, and 72 h after OVA challenge.


RESULTS
(1) The percentages of IFN-gamma(+)CD4(+), IFN-gamma(+)CD8(+) and IL-4(+)CD4(+) cells in the peripheral blood were significantly higher in the patients with acute exacerbation [(30% +/- 10%), (42% +/- 15%), and (4.2% +/- 1.6%) respectively] than those in the patients with remission asthma [(20% +/- 8%), (30% +/- 10%), and (2.0% +/- 0.8%) respectively, and P < 0.001;] and those in the normal subjects [(18% +/- 8%), and (24% +/- 9%), P < 0.01, and (1.9% +/- 0.9%), P < 0.001; respectively]. But all the parameters were not different significantly between the patients with remission asthma and the normal subjects. (2) In the asthmatic rat models, the IFN-gamma(+)CD4(+) cells in peripheral blood increased 2 h after OVA challenge (5.7% +/- 1.6%), and peaked 10 h after (9.9% +/- 4.4%), and decreased afterwards. The IFN-gamma(+)CD8(+) cells in peripheral blood increased 2 h after (11.5% +/- 5.1%) OVA challenge, and peaked 10 h after (38.7% +/- 6.3%), and then decreased afterwards. The IL-4(+)CD4(+) cells increased 2 h (1.7% +/- 1.0%) after OVA challenge, and peaked 36 h after (4.0% +/- 1.6%), and then decreased.


CONCLUSIONS
Both Th1 (IFN-gamma) and Th2 (IL-4) cytokines generated by peripheral blood mononuclear cells in asthma subjects and asthmatic rat models play a role in the development of airway inflammation in bronchial asthma dynamically. Th1 cytokines dominate at the early stage of airway inflammation, whereas Th2 cytokines achieves the major effects at later stage of the inflammation. It suggests that using different strategy in treatment of asthmatics in early stage and late stage may be necessary to control asthma.
Shi
Ju-Hong
JH
Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
Li
Tai-Sheng
TS
Lin
Yao-Guang
YG
D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000473:pathology*; D001991:Bronchitis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D011994:Recombinant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma