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*
Second Division, Department of Internal Medicine, and
Department of Microbiology and Immunology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan; and
Department of Internal Medicine, National Sanatorium of Tenryu Hospital, Hamakita, Shizuoka, Japan
Sensitized Brown Norway rats are known to develop eosinophilic
bronchial inflammation and airway hyperresponsiveness after Ag
exposure. However, we have previously observed that sensitized aged
rats of the same strain failed to develop such allergic inflammation.
In the present study, we investigated age-associated changes of
cytokine mRNA expression in bronchoalveolar lavage (BAL) cells. Both
young (8- to 10-wk-old) and aged (100- to 120-wk-old) Brown Norway rats
were sensitized with OVA, and BAL was performed 24 h after OVA
inhalation challenge. Semiquantitative RT-PCR analysis of BAL cells
showed that the cells from aged rats preferentially expressed Th1 type
cytokine (IFN-
) mRNA, whereas cells from young animals expressed
more Th2 type cytokine mRNAs including those for IL-4 and IL-5.
Decreased expression of Th2 type cytokine transcripts in aged animals
was further confirmed by quantitative analysis, competitive RT-PCR of
BAL cells, and in situ hybridization. The age-associated changes of
cytokine profile were not restricted to BAL cells but were a general
feature of lymphocytes, as shown by examination of popliteal lymph
nodes draining the site of sensitization. These findings suggest
that decreased allergic inflammation in aged animals is attributable to
age-dependent impairment of Th2 generation in response to
Ag.
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