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31.
D. Chabannes L. Vernillet D. Cantarovich H. Humbert H. Vie J. -P. Soulillou 《Transplant international》1990,3(4):189-194
The immunosuppressive effect of kidney graft recipient sera was studied on T-lymphocyte alloreactive line (4H) proliferation and compared to native cyclosporin A (CyA) and CyA metabolite concentrations determined by radioimmunoassay (RIA) using specific or nonspecific monoclonal antibodies. Three clinical groups were studied: (1) patients experiencing acute renal rejection episodes (CyA-R), (2) patients experiencing CyA-dependent nephrotoxicity episodes (CyA-TOX) and (3) patients in a clinically steady state (CyA-ST), according to their therapeutic regimen i.e., monotherapy (CyA alone) or polytherapy (CyA associated with prednisolone and/or azathioprine). Regardless of the clinical state, sera of patients in polytherapy displayed more inhibitory activity than those of monotherapy patients (24% and 40% inhibition of 4H proliferation, respectively, at sera dilution of 1:2), something which was no doubt due to the inhibitory activity of prednisolone on T-lymphocyte growth. In the two therapeutic regimens, CyA-ST patient sera exhibited the lowest inhibitory activity on the 4H line (45% and 65% inhibition of 4H proliferation in mono-and polytherapy, respectively, at sera dilution of 1:2). Sera from CyA-TOX patients were highly inhibitory (74% and 86% inhibition of 4H proliferation in mono-and polytherapy, respectively, at sera dilution of 1:2), in agreement with RIA assays showing increased native circulating CyA and CyA metabolites and daily CyA intake in this group as compared to CyA-St. Surprisingly, CyA-R patient sera were no less inhibitory than those of CyA-ST patients on 4H-line, antigen-induced proliferation. This clinical group did not differ from others for CyA intake or level of circulating immunosuppressive molecules, suggesting that rejection could be associated with a state of interindividual variation in sensitivity to CyA. In addition, a polytherapeutic regimen seemed to modify CyA bioavailability in CyA-ST group patients, with a decreased CyA metabolite level as compared to their monotherapy counterparts (native CyA plus metabolite/native CyA ratio being 2.73 and 3.73, respectively). In contrast, in the CyA-R patient group, polytherapy appeared to be associated with an increase in CyA metabolite circulating levels (ratio 4.79). In view of the low inhibitory activity of CyA metabolites, this profile might lead to rejection. 相似文献
32.
33.
Cyclosporine is a powerful immunosuppressant with a narrow therapeutic window and considerable inter- and intrapatient variability.
The pre-dose trough concentration (Cmin) is commonly used for therapeutic drug monitoring. With the new microemulsion (Neoral), intrapatient variability was reduced.
However, the usefulness of Neoral Cmin was questioned. Firstly, because of the improved and more-rapid absorption, accidental intake before blood sampling has a
greater impact on Cmin than with classic cyclosporine. Secondly, Cmin may be low despite high drug exposure, due to rapid clearance in children. A full pharmacokinetic (PK) profile with determination
of the area under the curve (AUC) is expensive and cumbersome, and therefore a search for an abbreviated AUC began. Here,
we present a retrospective analysis of 84 PK profiles from 78 pediatric renal transplant recipients. By analysis of rejection
episodes and toxicity, we estimated a target AUC above 5,000 ng×h/ml in the early post-transplant period and 3,900 ng×h/ml
beyond 100 days. The abbreviated AUC using the 2- and 6-h concentrations (C2 and C6) and a simple estimate derived from the
3-h concentration (C3) were equally well correlated with the AUC. From our data, we recommend a target C3 at approximately
800 ng/ml early after transplantation and 450–550 ng/ml beyond 100 days.
Received: 28 January 1998 / Revised: 10 June 1998 / Accepted: 15 June 1998 相似文献
34.
Michael T. Halpern 《Journal of clinical immunology》1991,11(1):1-12
Since the term lymphokine first appeared in print over 20 years ago, a tremendous number of these soluble mediators of the immune system have been described. Within the past few years, many human nonspecific suppressive lymphokines have been identified. This review discusses the historical basis of immunologic suppression and suppressor factors. Later reports describing suppressive human lymphokines are then grouped into four categories: primarily stimulatory lymphokines that also mediate certain suppressive activities, suppressive lymphokines produced during altered states of immunity, suppressive lymphokines produced by exogenously stimulated lymphocytes, and suppressive lymphokines produced by unstimulated lymphocytes. Recent work I have been involved in focusing on the human suppressive lymphokine soluble suppressor factor (SSF) is also discussed. 相似文献
35.
D. Kabelitz M. L. da Silva Lobo K. Pechhold 《Journal of molecular medicine (Berlin, Germany)》1991,69(13):623-628
Summary The clinical success of organ transplantation depends to a large degree on the immunological acceptance of the grafted organ. This paper summarizes from an immunological point of view the recent progress that has been made to improve graft acceptance, and discusses some future aspects in the field. Over the last few years, major emphasis has been put on the development of new immunosuppressive drugs, including FK 506, rapamycin, and Deoxyspergualin. Together with monoclonal antibodies against defined T-cell surface antigens, there are now new and effective means available to prevent or treat rejection episodes. Progress has also been made in the field of HLA typing, where the introduction of molecular biology-based methods significantly increased the accuracy of HLA class II typing. The ultimate goal of transplantation immunology is the induction of (donor-) specific tolerance. While some protocols are effective in inducing peripheral tolerance in experimental animals, these regimens are at present not yet applicable in the clinical situation. To overcome the shortage of donor organs, alternative strategies are currently being considered. Among these, xenotransplantation may eventually prove successful, despite the massive immunological problems such as, e.g., the presence of preformed xenoreactive antibodies.Abbreviations CTL
cytolytic T lymphocyte
- HLA
human leukocyte antigen
- MHC
major histocompatibility complex
- PCR
polymerase chain reaction
- mAB
monoclonal antibody
- RFLP
restriction fragment length polymorphism
- TCR
T-cell receptor
Preprint of a lecture to be read at the 22nd Congress of the Gesellschaft für Nephrologie, Heidelberg, September 15–18, 1991 (Editor: Prof. Dr. E. Ritz, Heidelberg) 相似文献
36.
Ken Ian Welsh 《Pediatric nephrology (Berlin, Germany)》1991,5(5):622-629
This article reviews recent papers relating to immunosuppressives and attempts to categorise the bewildering number of new reagents according to their effects on the immune response. It is apparent that the majority of groups are concentrating on reagents which, like cyclosporin A, are predominantly directed at T cells (42% of the last 200 papers inTransplantation, Transplant International andTransplantation Proceedings). The major change in strategy which is occurring relates to the rapidly increasing use of reagents directed against T cell subsets, especially those directed against the interleukin-2 receptor and CD4-positive T cells. This groups's share of the market has risen from 2% to over 12% within 5 years. New successful monoclonal antibodies include reagents directed against antigen-presenting cells and against molecules directly involved in cell adherence. The use of donor bone marrow or subsets of cells from donor bone marrow as inducers of non-reactivity, especially to solid organ grafts, is certainly one of the most exciting of the non-antibody protocols. It is encouraging that relatively specific immunosuppression can be induced in animals by combinations of specific and non-specific reagents as well as by specific reagents alone. This will facilitate the introduction of specific protocols into the human situation, and this strategy holds out great hope for the future. Unfortunately, one of the most effective ingredients of such combination therapies in animal models (anti-CD4) appears to have its tolerogenic potential abrogated by cyclosporin A and FK-506. One area of immunosuppression which is receiving scant interest relates to antibody (especially non human leucocyte antigen antibody) production, but as the interest in xenotransplantation increases it is anticipated that major new interest will emerge in this area. 相似文献
37.
目的 探讨肾移植术后泌尿系统肿瘤的发生情况、临床特点、诊断及治疗。方法 对本院自1991年~ 2 0 0 1年十年间行同种异体肾移植术 10 96例术后泌尿系统肿瘤的发生情况进行回顾性分析 ,并结合复习文献。结果 本组发现泌尿系统肿瘤 6例 ,发生率为 0 .5 5 %。其中肾盂癌 2例 (其中 1例为双侧肾盂癌 ) ,膀胱癌 1例 ,肾盂癌合并膀胱癌 2例 ,输尿管癌 1例。 6例均行手术治疗 ,平均随访11.4个月 ,效果良好。结论 肾移植术后出现血尿 ,除排斥反应外 ,还应注意泌尿系统肿瘤的可能性。 相似文献
38.
39.
雷公藤甲素对小鼠淋巴细胞体外活化的抑制作用 总被引:9,自引:1,他引:9
目的:研究雷公藤甲素(TRD)对小鼠T淋巴细胞活化标志CD69、CD25及细胞因子IL-2及IFN-γmRNA表达的影响,为阐明其免疫抑制作用提供分子药理学依据.方法:无菌分离小鼠淋巴结细胞,加入不同浓度的雷公藤甲素预先孵育1 h,用多克隆刺激剂刀豆蛋白(ConA)刺激T细胞活化,利用荧光标记的单克隆体双染技术,流式细胞仪检测TRD对小鼠T细胞CD69、CD25表达的影响;采用半定量RT-PCR技术从mRNA水平检测TRD对细胞因子IL-2、IFN-γ mRNA的表达的影响.结果:TRD能抑制T细胞早期活化标志CD69和CD25,同时TRD也能抑制IL-2及IFN-γmRNA的表达.结论:TRD对T细胞早期活化分子及细胞因子表达的抑制作用可能是其发挥免疫抑制作用的机制之一. 相似文献
40.