Sewell W A, Scurr L L, Orphanides H, Kinder S, Ludowyke R I
Centre for Immunology, University of New South Wales, and St. Vincent's Hospital, Sydney, Australia.
Clin Diagn Lab Immunol. 1998 Jan;5(1):18-23. doi: 10.1128/CDLI.5.1.18-23.1998.
Inflammation in asthma and other allergic diseases is characterized by excessive production of immunoglobulin E (IgE) and the influx of leukocytes, especially eosinophils. Interleukin 4 (IL-4) and IL-5 are essential for IgE production and eosinophilia, respectively, and are produced by mast cells in allergic conditions, for which glucocorticoids are widely used therapeutically. We assessed the effect of glucocorticoids on IL-4 and IL-5 mRNA production by the RBL-2H3 cell line, an analog of mucosal mast cells. IL-4 and IL-5 mRNAs were induced by an antigen that is used to cross-link receptor bound IgE, by calcium ionophore, or by ionophore with phorbol ester and were markedly inhibited by dexamethasone. In cells activated with ionophore and phorbol ester, 10(-6) M dexamethasone reduced the IL-4 and IL-5 mRNA levels to only 12.8 and 5.7%, respectively, of those in cells without dexamethasone, and 10(-9) M dexamethasone caused reductions to 27 and 56%, respectively. Hydrocortisone at 10(-6) and 10(-7) M almost completely inhibited IL-4 and IL-5 mRNA production. Dexamethasone was markedly inhibitory even if it was added after the cells were activated, provided that it was present in the cultures for at least 1.5 h. These studies indicate that the expression of IL-4 and IL-5 mRNAs by mast cells is highly sensitive to glucocorticoids. The data suggest that these inhibitory effects may contribute to the clinical efficacy of glucocorticoids in the therapy of allergic diseases.
哮喘和其他过敏性疾病中的炎症表现为免疫球蛋白E（IgE）过度产生以及白细胞尤其是嗜酸性粒细胞的流入。白细胞介素4（IL-4）和IL-5分别对IgE产生和嗜酸性粒细胞增多至关重要，且在过敏状态下由肥大细胞产生，糖皮质激素被广泛用于治疗这些疾病。我们评估了糖皮质激素对RBL-2H3细胞系（一种黏膜肥大细胞类似物）中IL-4和IL-5 mRNA产生的影响。IL-4和IL-5 mRNA可由用于交联受体结合IgE的抗原、钙离子载体或钙离子载体与佛波酯诱导产生，并被地塞米松显著抑制。在用离子载体和佛波酯激活的细胞中，10⁻⁶ M地塞米松将IL-4和IL-5 mRNA水平分别降至未用地塞米松细胞中的12.8%和5.7%，而10⁻⁹ M地塞米松则分别使其降至27%和56%。10⁻⁶和10⁻⁷ M的氢化可的松几乎完全抑制IL-4和IL-5 mRNA的产生。即使在地塞米松在细胞激活后添加，只要其在培养物中存在至少1.5小时，它仍具有显著抑制作用。这些研究表明肥大细胞中IL-4和IL-5 mRNA的表达对糖皮质激素高度敏感。数据表明这些抑制作用可能有助于糖皮质激素在过敏性疾病治疗中的临床疗效。
