Ohtani Tomoyuki, Aiba Setsuya, Mizuashi Masato, Kawamoto Yuji, Tagami Hachiro
Department of Dermatology, Tohoku Unviersity Graduate School of Medicine, Sendai, Japan.
J Am Acad Dermatol. 2003 Aug;49(2):234-42. doi: 10.1067/s0190-9622(03)01478-6.
It has been reported that histamine induces CD86 expression and chemokine production in human immature monocyte-derived dendritic cells (MoDCs), which can be blocked by both H(1)- and H(2)-receptor antagonists.
We sought to examine whether the efficacy of H(1)-type antihistamines can be assessed by using MoDCs.
We examined the suppressive effects of 1 H(2)-type antihistamine (cimetidine) and 5 different H(1)-type antihistamines (cetirizine, diphenhydramine, ketotifen, olopatadine, and emedastine) on the induction of CD86 and IL-8 production by MoDCs from 23 healthy individuals stimulated with histamine. We also examined the responses of MoDCs from 13 patients with chronic urticaria to these antihistamines, and compared the in vitro efficacy with the actual clinical response to antihistamines evaluated by patient and physician assessments.
All the antihistamines we examined suppressed the increase of CD86(+) cells after histamine stimulation in a dose-dependent fashion, and all H(1)-type antihistamines were more efficacious than cimetidine. IL-8 production stimulated with histamine was also suppressed by cetirizine, ketotifen, and olopatadine. Unexpectedly, the suppressive effect of these antihistamines on the CD86 augmentation was highly variable among different healthy control participants. Interestingly, in 10 of 13 cases of chronic urticaria, this in vitro analysis of antihistamines correlated with the clinical response to antihistamines.
This study suggests that the evaluation of antihistamines using MoDCs can be a useful method for the screening of effective antihistamines, for the comparison of the efficacy of antihistamines, and for predicting the efficacy of antihistamines on an individual basis.
据报道，组胺可诱导人未成熟单核细胞来源的树突状细胞（MoDCs）表达CD86并产生趋化因子，而H(1)和H(2)受体拮抗剂均可阻断这一过程。
我们试图研究是否可以利用MoDCs评估H(1)型抗组胺药的疗效。
我们检测了1种H(2)型抗组胺药（西咪替丁）和5种不同的H(1)型抗组胺药（西替利嗪、苯海拉明、酮替芬、奥洛他定和依美斯汀）对23名健康个体的MoDCs在组胺刺激下诱导CD86表达和产生IL-8的抑制作用。我们还检测了13例慢性荨麻疹患者的MoDCs对这些抗组胺药的反应，并将体外疗效与患者和医生评估的抗组胺药实际临床反应进行比较。
我们检测的所有抗组胺药均以剂量依赖方式抑制组胺刺激后CD86(+)细胞的增加，且所有H(1)型抗组胺药比西咪替丁更有效。西替利嗪、酮替芬和奥洛他定也抑制组胺刺激产生的IL-8。出乎意料的是，这些抗组胺药对CD86增加的抑制作用在不同健康对照参与者中差异很大。有趣的是，在13例慢性荨麻疹患者中的10例中，这种抗组胺药的体外分析与抗组胺药的临床反应相关。
本研究表明，利用MoDCs评估抗组胺药可能是筛选有效抗组胺药、比较抗组胺药疗效以及预测个体抗组胺药疗效的有用方法。
