Albanesi C, Pastore S, Fanales-Belasio E, Girolomoni G
Laboratory of Immunology, Istituto Dermopatico dell'Immacolata, IRCCS, Rome, Italy.
Clin Exp Allergy. 1998 Jan;28(1):101-9. doi: 10.1046/j.1365-2222.1998.00206.x.
Cetirizine is a H1 histamine antagonist which possesses anti-inflammatory properties through inhibition of leucocyte recruitment and activation, and reduction of ICAM-1 expression on mucosal epithelial cells. No studies have addressed the potential anti-inflammatory activities of cetirizine on skin keratinocytes.
Cetirizine and hydrocortisone were compared in their capacity to counteract human keratinocytes activation by IFNgamma. In particular, expression of immuno-modulatory membrane molecules and chemokine release have been examined.
Keratinocyte cultures established from normal skin of healthy donors were activated by IFNgamma (100-500 U/mL) in the absence or presence of cetirizine (10(-3)-10(3) microM) or hydrocortisone (10(-3)-10(2) microM), and tested for expression of ICAM-1, HLA-DR, MHC class I and CD40 as well as for release of RANTES, IL-8, macrophage chemotactic protein-1 (MCP-1) and granulocyte macrophage-colony stimulating factor (GM-CSF).
Cetirizine at high concentrations (10(2)-10(3) microM) markedly inhibited IFNgamma-induced expression of membrane ICAM-1, HLA-DR and up-regulation of MHC class I, but had no effect on CD40 expression. In contrast, hydrocortisone (10(2) microM) enhanced IFNgamma-induced membrane ICAM-1, reduced expression of HLA-DR and did not alter expression of MHC class I and CD40. Consistently, high doses of cetirizine decreased, whereas hydrocortisone increased, soluble ICAM-1 levels in the supernatants of IFNgamma-treated keratinocytes. The inhibiting and stimulating effects of cetirizine and hydrocortisone, respectively, on ICAM-1 expression were confirmed at the mRNA level by Northern blot analysis. Finally, cetirizine, but not hydrocortisone, inhibited the release of MCP-1 and RANTES from IFNgamma-stimulated keratinocytes. In contrast, hydrocortisone, but not cetirizine, reduced GM-CSF and IL-8 release.
The results indicate that cetirizine has the capacity to block the IFNgamma-induced activation of keratinocytes, and thus can exert important regulatory effects on TH1 cell-mediated immune responses in the skin. The high doses required for evidencing these activities suggest the potential benefits of a topical use of cetirizine.
西替利嗪是一种H1组胺拮抗剂，通过抑制白细胞募集和激活以及降低黏膜上皮细胞上细胞间黏附分子-1（ICAM-1）的表达而具有抗炎特性。尚无研究探讨西替利嗪对皮肤角质形成细胞的潜在抗炎活性。
比较西替利嗪和氢化可的松对抗γ干扰素（IFNγ）诱导的人角质形成细胞活化的能力。特别检测了免疫调节膜分子的表达和趋化因子的释放。
在不存在或存在西替利嗪（10⁻³ - 10³微摩尔）或氢化可的松（10⁻³ - 10²微摩尔）的情况下，用IFNγ（100 - 500单位/毫升）激活从健康供体正常皮肤建立的角质形成细胞培养物，并检测ICAM-1、人类白细胞抗原-DR（HLA-DR）、主要组织相容性复合体I类分子（MHC I类）和CD40的表达，以及检测调节活化正常T细胞表达和分泌的趋化因子（RANTES）、白细胞介素-8（IL-8）、巨噬细胞趋化蛋白-1（MCP-1）和粒细胞巨噬细胞集落刺激因子（GM-CSF）的释放。
高浓度（10² - 10³微摩尔）的西替利嗪显著抑制IFNγ诱导的膜ICAM-1、HLA-DR表达以及MHC I类分子的上调，但对CD40表达无影响。相比之下，氢化可的松（10²微摩尔）增强IFNγ诱导的膜ICAM-1表达，降低HLA-DR表达，且不改变MHC I类分子和CD40的表达。同样，高剂量西替利嗪降低了IFNγ处理的角质形成细胞上清液中可溶性ICAM-1水平，而氢化可的松则使其升高。通过Northern印迹分析在mRNA水平证实了西替利嗪和氢化可的松分别对ICAM-1表达的抑制和刺激作用。最后，西替利嗪而非氢化可的松抑制了IFNγ刺激的角质形成细胞释放MCP-1和RANTES。相反，氢化可的松而非西替利嗪降低了GM-CSF和IL-8的释放。
结果表明西替利嗪有能力阻断IFNγ诱导的角质形成细胞活化，因此可对皮肤中Th1细胞介导的免疫反应发挥重要调节作用。证明这些活性所需的高剂量提示了局部使用西替利嗪的潜在益处。
