Bemelman F J, Jansen J, van der Poll T, van Deventer S J, ten Berge R J
University of Amsterdam, Department of Internal Medicine, The Netherlands.
Nephrol Dial Transplant. 1994;9(12):1786-90.
The use of OKT3 is associated with severe clinical side-effects. Adverse reactions are partly attributed to release of tumour necrosis factor (TNF). TNF binds to two receptors on the outer membranes of most human cell lines. Shedding of these proteins (sTNFR-p55 and sTNFR-p75) may block biological effects of TNF. Here we show a fair correlation between serum levels of sTNFRs and renal function as measured by glomerular filtration rate (GFR). In addition we assessed levels of sTNFR-p55 and sTNFR-p75, corrected for reduced renal clearance, in renal allograft rejection and following treatment with OKT3. Corrected serum levels (CSL) of sTNFR-p55 and sTNFR-p75 were determined in 12 renal allograft patients treated for an acute rejection episode with either OKT3 or methylprednisolone (MPNS). Serum levels of CSLsTNFR-p55 and CSLsTNFR-p75 in both groups prior to anti-rejection treatment were not elevated. CSLsTNFRs peaked at 1 h after the administration of OKT3, whereas in the MPNS group CSLsTNFRs remained unchanged. We conclude that in acute renal transplant rejection CSLsTNFRs increase after treatment with OKT3. In spite of high circulating sTNFRs levels all OKT3-treated patients suffered from clinical side-effects.
OKT3 的使用与严重的临床副作用相关。不良反应部分归因于肿瘤坏死因子（TNF）的释放。TNF 与大多数人类细胞系外膜上的两种受体结合。这些蛋白质（可溶性肿瘤坏死因子受体 p55 和可溶性肿瘤坏死因子受体 p75）的脱落可能会阻断 TNF 的生物学效应。在此我们发现，可溶性肿瘤坏死因子受体的血清水平与通过肾小球滤过率（GFR）测量的肾功能之间存在一定的相关性。此外，我们评估了肾移植排斥反应及 OKT3 治疗后经肾清除率校正的可溶性肿瘤坏死因子受体 p55 和可溶性肿瘤坏死因子受体 p75 的水平。在 12 例接受 OKT3 或甲泼尼龙（MPNS）治疗急性排斥反应的肾移植患者中，测定了经校正的可溶性肿瘤坏死因子受体 p55 和可溶性肿瘤坏死因子受体 p75 的血清水平（CSL）。两组在抗排斥治疗前，经校正的可溶性肿瘤坏死因子受体 p55 和经校正的可溶性肿瘤坏死因子受体 p75 的血清水平均未升高。经校正的可溶性肿瘤坏死因子受体水平在给予 OKT3 后 1 小时达到峰值，而在甲泼尼龙组中，经校正的可溶性肿瘤坏死因子受体水平保持不变。我们得出结论，在急性肾移植排斥反应中，使用 OKT3 治疗后经校正的可溶性肿瘤坏死因子受体水平会升高。尽管循环中的可溶性肿瘤坏死因子受体水平很高，但所有接受 OKT3 治疗的患者都出现了临床副作用。
