2nd Pharmacology, Drug Development Laboratories I, Fujisawa Pharmaceutical Co., 2-1-6 Kashima, Yodogawa-ku, Osaka, 532, Japan.
Mediators Inflamm. 1997;6(5-6):369-74. doi: 10.1080/09629359791514.
Anti-inflammatory actions of two anti-allergic drugs, alone or with dexamethasone (Dex) were examined in two models, because inflammation is claimed to be important for allergic events, especially for asthma. Cromoglycate and nedocromil were tested in ischaemic- and histamineinduced paw oedema models of mice. These antiallergic drugs (1-100 mg/kg, i.p.) failed to suppress these oedemata, but enhanced the suppressions by a low dose of dexamethasone (0.1 mg/kg, s.c.) at 3-8 h after Dex injection. The mode of effects by anti-allergic drugs resembled that of a natural antioxidant (alpha-tocopherol, beta-carotene etc.), and was different from that of an immunosuppressant like FK506. The enhancing potencies of the two anti-allergic drugs were similar at 6 h after Dex in both oedemata, and were diminished by superoxide dismutase (SOD) or catalase (i.p.). Cycloheximide completely abolished suppressions. Nedocromil, but not cromoglycate, inhibits inflammatory events. Therefore, there are common unknown actions by which the two anti-allergics enhance suppression by Dex. A possible mechanism of this action was supposed to enhance the superoxide and/or hydrogen peroxide-dependent glucocorticoid receptor (GR) signalling in the target cells.
两种抗过敏药物（单独使用或与地塞米松（Dex）联合使用）的抗炎作用在两种模型中进行了研究，因为炎症被认为对过敏事件很重要，尤其是对哮喘。色甘酸和奈多罗米在缺血性和组胺诱导的小鼠爪肿胀模型中进行了测试。这些抗过敏药物（1-100mg/kg，ip）未能抑制这些肿胀，但在 Dex 注射后 3-8 小时增强了低剂量地塞米松（0.1mg/kg，sc）的抑制作用。抗过敏药物的作用方式类似于天然抗氧化剂（α-生育酚、β-胡萝卜素等），与免疫抑制剂如 FK506 不同。在两种肿胀中，两种抗过敏药物在 Dex 后 6 小时的增强效力相似，并且被超氧化物歧化酶（SOD）或过氧化氢酶（ip）减弱。环磷酰胺完全消除了抑制作用。奈多罗米，但不是色甘酸，抑制炎症事件。因此，两种抗过敏药物通过未知的共同作用增强了 Dex 的抑制作用。这种作用的一种可能机制是增强靶细胞中超氧阴离子和/或过氧化氢依赖性糖皮质激素受体（GR）信号转导。
