Evidence that cyclosporin A and dexamethasone inhibit allergic airway eosinophilic inflammation via suppression of interleukin-5 synthesis by T cells.
1. We have recently demonstrated that airway eosinophilic inflammation can be transferred to unprimed mice by infusing interleukin (IL)-5-producing T cell clones. Using that murine model, we performed this study to delineate the mechanism of cyclosporin A and dexamethasone to inhibit allergic airway eosinophilic inflammation. 2. The ovalbumin-reactive murine T cell clones, FJ17, produced IL-2, IL-4 and IL-5 upon stimulation with relevant antigen. In FJ17-transferred mice, messenger RNA (mRNA) of IL-2 and IL-5 expressed in the lungs, the number of eosinophils in bronchoalveolar lavage fluid (BALF) was increased and the bronchial responsiveness to acetylcholine was enhanced after antigen provocation. 3. Cyclosporin A (10, 100 ng ml(-1)) and dexamethasone (10, 100 ng ml(-1) suppressed the production of IL-5 as well as IL-2 and IL-4 by FJ17 in vitro. 4. Subcutaneously administered cyclosporin A (30 mg kg(-1)) and dexamethasone (10 mg kg(-1)) inhibited antigen-induced mRNA expression of IL-2 and IL-5, increase of BALF eosinophils and bronchial hyperresponsiveness of FJ17-transferred mice in vivo. The number of BALF eosinophils was correlated with the bronchial responsiveness to acetylcholine (r=0.672). 5. The results clearly indicated that the suppression of IL-5 synthesis by T cells is involved in the effects of cyclosporin A and dexamethasone to inhibit allergic airway eosinophilic inflammation.
Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd., Toda, Saitama, Japan.
A
A
Nakata
O
O
Kaminuma
A
A
Mori
K
K
Ogawa
H
H
Kikkawa
K
K
Naito
K
K
Ikezawa
M
M
Suko
H
H
Okudaira
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000378:metabolism / Q000517:prevention & control*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004802:Eosinophilia / Q000378:metabolism / Q000517:prevention & control*; D006967:Hypersensitivity / Q000378:metabolism / Q000517:prevention & control*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D015848:Interleukin-5 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
D007376:Interleukin-2; D015848:Interleukin-5; D015847:Interleukin-4; D003907:Dexamethasone; D016572:Cyclosporine