Immunomodulatory effect of procainamide in man. Inhibition of human suppressor T-cell activity in vitro.

Immunomodulatory effect of procainamide in man. Inhibition of human suppressor T-cell activity in vitro.
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普鲁卡因酰胺对人体的免疫调节作用。

DOI:
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发表时间:
1983
影响因子:
15.9
通讯作者:
M. Ziff
M. Ziff
中科院分区:
医学1区
文献类型:
--
作者:
T. Ochi;E. Goldings;P. Lipsky;M. Ziff

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普鲁卡因胺(PA)在高比例的治疗个体中诱导多种自身抗体的产生,并且在某些个体中诱导与系统性红斑狼疮非常相似的综合征。PA这种作用的机制尚不清楚。为了检查PA可能通过改变正常免疫调节机制诱导自身抗体形成的可能性,检查了该药物对人体抗体形成的体外模型的作用。PA被发现,以增加免疫球蛋白分泌细胞(ISC)从人外周血单个核细胞(PBM)在商陆有丝分裂原的响应,但商陆有丝分裂原诱导的氚化胸苷掺入没有影响。当使用纯化的B和T细胞群时,PA增强了未处理的T细胞支持的B细胞培养物中ISC的产生,但丝裂霉素C处理的T细胞则没有。这些结果表明PA通过抑制抑制性T细胞活性而不是通过增强辅助性T细胞或B细胞功能来增强B细胞应答。N-乙酰普鲁卡因酰胺对ISC的产生没有影响。PA对伴刀豆球蛋白A(Con A)诱导的抑制细胞活性的影响也进行了检查,以确定PA是否改变抑制T细胞功能的产生或表达。将PBM与30微克/ml的Con A培养48小时以产生抑制细胞。当这些与新鲜PBM共培养时,产生的ISC的数量减少了58.1 +/- 3.4%(平均值+/- SEM,n = 6)。在没有Con A的情况下类似孵育的细胞没有抑制作用。在Con A刺激的培养物中加入PA抑制了抑制细胞的产生,这一事实表明,与Con A刺激的细胞共培养的新鲜细胞的反应仅减少了27.2 +/-4.3%。在这个系统中,N-乙酰基-普鲁卡因胺也没有影响。相比之下,PA仅加入到Con A刺激的细胞与新鲜PBM的共培养物中,对抑制细胞功能的影响不太明显。这些结果表明,PA的主要作用是抑制抑制性T细胞活性的产生。这种效应可以解释这种药物在治疗个体中诱导自身抗体形成的能力。
Procainamide (PA) induces the production of a number of autoantibodies in a high proportion of treated individuals and in some a syndrome closely resembling systemic lupus erythematosus. The mechanism underlying this action of PA is unclear. To examine the possibility that PA might induce autoantibody formation by altering normal immunoregulatory mechanisms, the action of this drug on an in vitro model of antibody formation in man was examined. PA was found to augment the generation of immunoglobulin-secreting cells (ISC) from human peripheral blood mononuclear cells (PBM) in response to pokeweed mitogen but had no effect on pokeweed mitogen-induced tritiated thymidine incorporation. When purified populations of B and T cells were used, PA enhanced the generation of ISC in B-cell cultures supported by untreated T cells but not by T cells treated with mitomycin C. These results indicate that PA augmented B-cell responses by inhibiting suppressor T-cell activity and not by augmenting helper T-cell or B-cell function. N-Acetyl-procainamide had no effect on the generation of ISC in this system. The effect of PA on concanavalin A (Con A)-induced suppressor cell activity was also examined to determine whether PA altered the generation or expression of suppressor T-cell function. PBM were cultured with 30 microgram/ml of Con A for 48 h to generate suppressor cells. When these were co-cultured with fresh PBM, the number of ISC generated was decreased by 58.1 +/- 3.4% (mean +/- SEM, n = 6). Cells that had been similarly incubated without Con A were not inhibitory. The addition of PA to the Con A-stimulated cultures inhibited the generation of suppressor cells as indicated by the fact that the response of fresh cells co-cultured with the Con A-stimulated cells was diminished by only 27.2 +/- 4.3%. In this system too, N-acetyl-procaimamide had no effect. By contrast, adding PA only to the co-culture of Con A-stimulated cells with fresh PBM had a less marked effect on suppressor cell function. These results indicate that the major action of PA is to inhibit the generation of suppressor T-cell activity. Such an effect may explain the capacity of this agent to induce autoantibody formation in treated individuals.
药物性狼疮:一种辅助性疾病?
DOI: 10.1016/0002-9343(81)90250-3
发表时间: 1981
期刊: The American journal of medicine
影响因子: --
作者:
Schoen,RT;Trentham,DE
通讯作者: Trentham,DE