Furue M, Osada A, Chang C H, Tamaki K
Department of Dermatology, Yamanashi Medical University, Japan.
J Invest Dermatol. 1994 Jul;103(1):49-53. doi: 10.1111/1523-1747.ep12389548.
Azelastine hydrochloride (AZE) is an anti-allergic drug that inhibits the release of various chemical mediators from mast cells. We compared the immunosuppressive effects of AZE and FK-506 in vivo and in vitro. Topical application of AZE strongly inhibited the efferent phase of contact hypersensitivity, as did application of FK-506. In in vitro experiments, we found that 1) the suppression by AZE on interleukin (IL)-2 production from splenic T cells was partial and considerably large amounts of IL-2 were still produced, even in the presence of 10(-5) M of AZE, which was in sharp contrast to the observed marked inhibition of [3H]-TdR incorporation; 2) AZE significantly inhibited the phorbol myristate acetate-induced IL-2 responsiveness; 3) AZE did not inhibit the IL-2 receptor alpha expression of activated T cells; and 4) the significant inhibitory action was still observed even when AZE was added at 48 h after the initiation of culture. In regard to FK-506, we found that 1) FK-506 completely blocked the production of IL-2; 2) exogeneous IL-2 consistently restored the FK-506-induced inhibition; 3) FK-506 affected the phorbol myristate acetate-induced IL-2 responsiveness very little, if any; and 4) the significant suppression was observed only when FK-506 was added within 24 h after the initiation of culture. Thus, AZE exerts its in vitro immunosuppressive activity preferentially by interfering with the IL-2 responsiveness, with partial inhibition of IL-2 production. Conversely, FK-506 acts as a strong inhibitor of IL-2 production without a prominent effect on IL-2 responsiveness. The immunosuppressive activity of AZE shown in vitro may also be operative in vivo and may be applicable for topical use.
盐酸氮卓斯汀（AZE）是一种抗过敏药物，可抑制肥大细胞释放多种化学介质。我们比较了AZE和FK - 506在体内和体外的免疫抑制作用。局部应用AZE强烈抑制接触性超敏反应的传出相，FK - 506的应用也是如此。在体外实验中，我们发现：1）AZE对脾T细胞白细胞介素（IL）-2产生的抑制是部分性的，即使存在10^(-5) M的AZE，仍会产生大量的IL - 2，这与观察到的对[3H]-TdR掺入的显著抑制形成鲜明对比；2）AZE显著抑制佛波酯肉豆蔻酸酯诱导的IL - 2反应性；3）AZE不抑制活化T细胞的IL - 2受体α表达；4）即使在培养开始后48小时添加AZE，仍观察到显著的抑制作用。关于FK - 506，我们发现：1）FK - 506完全阻断IL - 2的产生；2）外源性IL - 2持续恢复FK - 506诱导的抑制；3）FK - 506对佛波酯肉豆蔻酸酯诱导的IL - 2反应性影响极小（如果有影响的话）；4）仅在培养开始后24小时内添加FK - 506时才观察到显著的抑制作用。因此，AZE优先通过干扰IL - 2反应性发挥其体外免疫抑制活性，并部分抑制IL - 2的产生。相反，FK - 506是IL - 2产生的强抑制剂，对IL - 2反应性没有显著影响。AZE在体外显示的免疫抑制活性在体内可能也起作用，并且可能适用于局部使用。
