J Asthma Allergy Clin Immunol.
1999 Feb;19(1):79-90.
Effect of interleukin-12 on airway inflammation in mouse model of bronchial asthma
Abstract
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BACKGROUND: Th2-like cells are thought to play a crucial role in the recruitment and
activation of eosinophil in bronchial asthma. In contrast to Th2 cytokine, Thl cytokine
IFN-y decreases eosinophil recruitment. Previous studies have shown that IL-12 promotes
differentiation of Th0 into Thl and enhances production of Thl cytokine. IL-12 also
prevents differentiation of Th0 into Th2 during primary immune response. Its effect
on established Th2 cell, however, is well known.
OBJECTIVE
The objective of aur study was focused on whether IL-12 prevents recruitment
of eosinophil and expression of Th2 cytokine in murine model for bronchial asthma, and
whether its effect differs according to timing of dosage.
METHOD: Administration of IL-12 was tested in the 3 different time-frames; 1) allergic
sensitization (early dosage) 2) allergic challenge (late doaage) or 3) both. The number
of eosinophil in the bronchoalveolar lavage(BAL) fluid and tissue was examined for change
of airway inflammation. The effect on cytokine expression was assessed by measuring
cytokine in bronchoalveolar lavage fluid (ELISA) and mRNA in peribronchial lymph node (RT-PCR)
RESULTS
Early dosage of IL-12, and the combination of early and late dosages, strikingly
decreased the numbers of eosinophil in both BAL fluid and tissue(p<0.05). Late dosage
of IL-12 decreased tissue eosinophilia, while the number of eosinophil in BAL fluid
remained unchanged. IL-12 increased IL-4 and IL-5 levels, and decreased IL-2 and I~FN-r
levels. There were no differences in Thl/Th2 cytokine regulation among the three dosage
times. Early dosage of IL-12, and the combination of early and late dosages, increased
IL-10 level, but late dosage had no effect on IL-10.
CONCLUSION
These results demonstrate that depending upon whether IL-12 is administered
during sensitization or during subsequent allergen exposure, Thl/Th2 cytokine regulation
by IL -12 shows no difference because it seems that difference of inhibition of eosinophil
recruitment by IL-12 might be related with the other factors, such as IL-10.