OKT3 1ST-DOSE REACTION - ASSOCIATION WITH T-CELL SUBSETS AND CYTOKINE RELEASE
OKT3 1ST-DOSE REACTION - ASSOCIATION WITH T-CELL SUBSETS AND CYTOKINE RELEASE
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DOI：
10.1038/ki.1991.18
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发表时间：
1991-01-01
影响因子：
19.6
通讯作者：
CURTIS, JJ
中科院分区：
文献类型：
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作者：
GASTON, RS;DEIERHOI, MH;CURTIS, JJ
OKT 3首次给药反应：与T细胞亚群和细胞因子释放相关使用单克隆抗体OKT 3来预防或治疗同种异体移植物排斥已经变得司空见惯。它的管理往往是复杂的严重副作用，通常发生在一至两个小时后给予OKT 3，并被称为首次剂量反应。这些体征和症状的机制尚不清楚，但可能与细胞因子释放有关。23名肾或肾/胰腺移植受者接受OKT 3治疗急性排斥反应。观察并前瞻性定量首次给药后出现的体征和症状，并计算反应评分。在首次OKT 3给药前即刻、给药后2小时和24小时抽血，测定白细胞介素-2（IL-2）、干扰素-γ（IFNγ）和肿瘤坏死因子-α（TNFα）水平，并对T细胞亚群进行流式细胞术分析。根据首次给药反应的严重程度定义两组。第1组患者（N = 11）的反应非常轻微（反应评分≤ 3）;第2组患者（N = 12）的反应更严重（评分≥ 5）。所有患者在OKT 3后2小时的血清TNF a水平均从基线显著升高（9 ± 3 pg/ml至378 ± 54 pg/ml，P < 0.0001），反应评分与2小时TNF a水平之间存在显著相关性（P = 0.005）。第2组患者在2小时时的TNF α水平高于第1组患者（484 ± 75 pg/ml vs. 263 ± 62 pg/ml，P = 0.04）。在任何采样时间，IL 2和IFNγ水平均未升高。在OKT 3给药前，第2组患者的循环CD 3+（521 ± 114 vs. 257 ± 58，P = 0.04）和CD 4+（226 ± 45 vs. 87 ± 23，P = 0.01）淋巴细胞数量也显著增加。此外，OKT 3前CD 4+水平与反应评分相关。这些数据暗示TNFα，可能是活化的T淋巴细胞来源，是OKT 3首次给药反应的关键介质。
OKT3 first-dose reaction: Association with T cell subsets and cytokine release. Use of the monoclonal antibody OKT3 to prevent or treat allograft rejection has become commonplace. Its administration is often complicated by serious side effects, usually occurring within one to two hours after OKT3 is given, and is termed first-dose reaction. The mechanism underlying these signs and symptoms is poorly defined, but may be related to cytokine release Twenty-three kidney or kidney/ pancreas transplant recipients received OKT3 as treatment of acute rejection. Signs and symptoms occurring after the first dose were observed and quantitated prospectively, and a reaction score was calculated. Blood was drawn immediately before, and at 2 and 24 hours after the first dose of OKT3 for determination of interleukin-2 (IL2), interferon-gamma (IFNγ), and tumor necrosis factor-alpha (TNFα) levels, and flow cytometric analysis of T cell subsets. Two groups were defined based on severity of first-dose reaction. Group 1 patients (N = 11) had very mild reactions (reaction score ≤ 3); Group 2 patients (N = 12) had more severe reactions (score ≥ 5). All patients demonstrated a significant rise in serum TNFa from baseline to two hours after OKT3 (9 ± 3 pg/ml to 378 ± 54 pg/ml, P < 0.0001), and there was significant correlation between reaction scores and two-hour TNFa levels (P = 0.005). Group 2 patients had higher TNFa levels at two hours than did Group 1 patients (484 ± 75 pg/ml vs. 263 ± 62 pg/ml, P = 0.04). Levels of IL2 and IFNγ were not elevated at any sampling time. Group 2 patients also had significantly greater numbers of circulating CD3+ (521 ± 114 vs. 257 ± 58, P = 0.04) and CD4+ (226 ± 45 vs. 87 ± 23, P = 0.01) lymphocytes prior to OKT3 administration. In addition, pre-OKT3 CD4+ levels correlated with reaction scores. These data implicate TNFα, perhaps of activated T lymphocyte origin, as a key mediator of the OKT3 first-dose reaction.