Buysmann S, van Diepen F N, Surachno S, Pals S T, ten Berge R J
University of Amsterdam, Department of Internal Medicine, The Netherlands.
Clin Nephrol. 1996 Aug;46(2):84-91.
OKT3 induces a systemic release of cytokines and a profound peripheral lymphocytopenia. In vitro, tumor necrosis factor-alpha, interleukin-1, and interferon-gamma increase adhesion molecule expression on vascular endothelium. To investigate the effects of OKT3 induced cytokine release on endothelial- and lymphocyte adhesion molecule expression in vivo, we studied sequential skin biopsies of six renal allograft recipients treated for acute rejection with 5 mg OKT3. An additional group of six patients treated for acute rejection with 50 mg methylprednisolone served as a control group. Compared to pre-treatment biopsies, biopsies taken 4.5- and 24 hours after the first OKT3 dose showed a maximal increase in VCAM-1 and ICAM-1 expression, respectively. In parallel, an increased number of CD2+, CD11a+, and CD49d+ mononuclear cells in the skin was observed in all OKT3 treated patients. No changes were observed after methylprednisolone treatment. We conclude that the OKT3 induced cytokine release induces increased ICAM-1- and VCAM-1 expression on vascular endothelium, leading to increased influx of CD2+ lymphocytes which may contribute to the peripheral lymphocytopenia after OKT3.
OKT3可诱导细胞因子的全身释放以及严重的外周淋巴细胞减少。在体外，肿瘤坏死因子-α、白细胞介素-1和干扰素-γ可增加血管内皮细胞上黏附分子的表达。为了研究OKT3诱导的细胞因子释放在体内对内皮细胞和淋巴细胞黏附分子表达的影响，我们对6例接受5mg OKT3治疗急性排斥反应的肾移植受者进行了连续的皮肤活检。另外6例接受50mg甲泼尼龙治疗急性排斥反应的患者作为对照组。与治疗前的活检相比，首次给予OKT3剂量后4.5小时和24小时所取的活检分别显示VCAM-1和ICAM-1表达最大程度增加。同时，在所有接受OKT3治疗的患者中，皮肤中CD2 +、CD11a +和CD49d +单核细胞数量增加。甲泼尼龙治疗后未观察到变化。我们得出结论，OKT3诱导的细胞因子释放可诱导血管内皮细胞上ICAM-1和VCAM-1表达增加，导致CD2 +淋巴细胞流入增加，这可能是OKT3后外周淋巴细胞减少的原因。
