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隔日泼尼松疗法与人类淋巴细胞亚群

Alternate-day prednisone therapy and human lymphocyte subpopulations.

作者信息

Fauci A S, Dale D C

出版信息

J Clin Invest. 1975 Jan;55(1):22-32. doi: 10.1172/JCI107914.

Abstract

The mechanisms and kinetics of the immunosuppressive effects of alternate-day prednisone were investigated in a group of patients with a variety of inflammatory diseases receiving a range of alternate-day prednisone doses from 5 to 120 mg. Total circulating lymphocyte and monocyte counts, as well as proportions of lymphocyte subpopulations defined both by surface markers and by in vitro functional capacities, were studied. At 8 a. m. of the day on prednisone, just before drug administration, lymphocyte and monocyte counts, proportions of lymphocyte subpopulations, as well as in vitro lymphocyte blastogenic responses to various mitogenic and antigenic stimuli were normal. 4 h after the administration of prednisone, there was a profound lymphocytopenia and monocytopenia, with a differential depletion of thymus-derived lymphocytes as well as various functionally defined lymphocyte subpopulations. Lymphocyte kinetic studies using a radioactive chromium-labeled autologous lymphocytes showed that the lymphocytopenia was due predominantly to a transient depletion of the recirculating portion of the intravascular lymphocytepool. All these parameters returned to normal by 8 a.m. of the following day (off prednisone) and remained normal throughout the day. This very transient lymphocytopenia and monocytopenia after prednisone, with normal cell numbers, proportions, and functions throughout the remainder of the 2-day cycle, was associated with suppression of disease activity, yet did not affect cutaneous delayed hypersensitivity in these patients nor increase the likelihood of infectious complications. This drug-associated cyclic and transient monocytopenia and selective lymphocytopenia is best explained by a redistribution of recirculating lymphocytes to other body compartments, particularly the bone marrow.

摘要

在一组患有各种炎症性疾病、接受5至120毫克不等隔日泼尼松剂量的患者中,研究了隔日泼尼松免疫抑制作用的机制和动力学。研究了外周血淋巴细胞和单核细胞总数,以及通过表面标志物和体外功能能力定义的淋巴细胞亚群比例。在服用泼尼松当天上午8点,即给药前,淋巴细胞和单核细胞计数、淋巴细胞亚群比例以及体外淋巴细胞对各种有丝分裂原和抗原刺激的增殖反应均正常。服用泼尼松4小时后,出现严重的淋巴细胞减少和单核细胞减少,胸腺来源的淋巴细胞以及各种功能定义的淋巴细胞亚群出现差异性减少。使用放射性铬标记的自体淋巴细胞进行的淋巴细胞动力学研究表明,淋巴细胞减少主要是由于血管内淋巴细胞池循环部分的短暂减少。所有这些参数在第二天上午8点(停用泼尼松)恢复正常,并在一整天保持正常。泼尼松后这种非常短暂的淋巴细胞减少和单核细胞减少,在2天周期的其余时间细胞数量、比例和功能均正常,与疾病活动的抑制相关,但不影响这些患者的皮肤迟发型超敏反应,也不增加感染并发症的可能性。这种与药物相关的周期性和短暂性单核细胞减少和选择性淋巴细胞减少,最好的解释是循环淋巴细胞重新分布到身体的其他部位,特别是骨髓。

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