Kimata M, Abe T, Yamaguchi I, Mito K, Tsunematsu M, Inagaki N, Nagai H
Department of Pharmacology, Gifu Pharmaceutical University, Gifu, Japan.
Pharmacology. 2001 Jan;62(1):17-22. doi: 10.1159/000056067.
Epicutaneous antigen challenge in passively sensitized mice with IgE produces a biphasic cutaneous response which peaks 1 h (immediate-phase reaction) and 24 h (late-phase reaction; LPR) after the antigen challenge. In this model, anaphylactic degranulation and interleukin 6 (IL-6) expression between 4 and 8 h are observed in resident mast cells as the preceding stage of LPR. Prednisolone at a dose of 3 mg kg(-1) clearly inhibited the LPR when administered 2 h before and 4 h after antigen challenge. Slight or no inhibition of LPR was observed by prednisolone administered 6-12 h after challenge. Histologically, prednisolone treatment 2 h before antigen challenge completely inhibited edema and inflammatory cell infiltration, while treatment at 6 h did not at all. In order to investigate the relationship between inhibition of LPR by prednisolone and mast cell activation, the effects of prednisolone on degranulation of mast cells and IL-6 expression in mast cells were investigated. 8 h after antigen challenge, prednisolone clearly inhibited the increase in the number of anaphylactic degranulated and IL-6-positive mast cells by administration 2 h before challenge, but did not affect it by administration 6 h after challenge. These data indicate that the inhibitory mechanism of prednisolone on LPR, at least, involves the inhibition of mast cell activation before LPR.
用IgE对被动致敏小鼠进行表皮抗原激发,会产生双相皮肤反应,该反应在抗原激发后1小时(速发相反应)和24小时(迟发相反应;LPR)达到峰值。在该模型中,作为LPR的前期阶段,在4至8小时可观察到驻留肥大细胞出现过敏样脱颗粒和白细胞介素6(IL-6)表达。当在抗原激发前2小时和激发后4小时给予剂量为3 mg kg(-1)的泼尼松龙时,可明显抑制LPR。在激发后6至12小时给予泼尼松龙,观察到对LPR的抑制作用轻微或无抑制作用。组织学上,在抗原激发前2小时给予泼尼松龙治疗可完全抑制水肿和炎性细胞浸润,而在6小时给予治疗则完全没有效果。为了研究泼尼松龙对LPR的抑制作用与肥大细胞活化之间的关系,研究了泼尼松龙对肥大细胞脱颗粒和肥大细胞中IL-6表达的影响。在抗原激发后8小时,泼尼松龙在激发前2小时给药可明显抑制过敏样脱颗粒和IL-6阳性肥大细胞数量的增加,但在激发后6小时给药则无此作用。这些数据表明,泼尼松龙对LPR的抑制机制至少涉及在LPR之前抑制肥大细胞活化。