Jurincic-Winkler C D, Gallati H, Alvarez-Mon M, Sippel J, Carballido J, Klippel K F
Department of Urology, General Hospital Celle, Germany.
Eur Urol. 1995;28(4):334-9. doi: 10.1159/000475077.
Intravesical instillation of keyhole limpet hemocyanin (KLH) is a possible treatment for decreasing tumor recurrence after transurethral resection (TUR) in patients with superficial transitional cell carcinoma of the bladder (stages pTa-pT1, grades 1-3). Our study confirms the theory that instillation of KLH stimulates production of cytokines, resulting in their secretion in urine. Interleukin-1 (IL-1) stimulates the immune cascade through a domino effect and is produced mainly by activated macrophages. The instillation program was started 5-7 days after TUR of primary superficial cell carcinoma. 20 mg KLH in 20 ml of 0.9% NaCl was instilled into the bladder each week for 6 consecutive weeks and then monthly for 1 year. When KLH is instilled into the bladder, IL-1 alpha is secreted in the urine. A specific enzyme-linked immunosorbent assay (ELISA) was used for analysis. The ELISA for IL-1 alpha was established in our laboratory and showed a detection limit of 5 pg/ml. This IL-1 alpha ELISA deviation amounts to 3-7% within a series of measurements, and 5-15% from series to series. In the therapy group the IL-1 alpha secretion ranged from 0 to 30,905 pg/24 h and in the control group from 0 (collection period) to 2,472 pg/4 h. IL-1 alpha production increased significantly after KLH instillation in bladder cancer patients; however, the level varied considerably from patient to patient. Maximum production was achieved within a period of 4-8 h, decreasing within 24 h. There was a striking difference between the amount of IL-1 alpha produced over the 24-hour period in the control group and that of the KLH group. 8 of 14 patients (57%) who responded to KLH therapy had higher urine IL-1 alpha levels after 6 weeks of KLH treatment than those who failed to respond within 12 months, but the levels were not of statistical significance. The secretion of IL-1 alpha in urine is the biological response of the bladder to the antigen stimulus of KLH. No IL-2 was detected in the urine samples. It remains to be determined whether no IL-2 cytokine was present, or whether the amount was smaller than the minimal detection limit required for the ELISA.
膀胱内灌注匙孔血蓝蛋白（KLH）可能是一种治疗方法，用于降低膀胱浅表性移行细胞癌（pTa - pT1期，1 - 3级）患者经尿道切除（TUR）术后的肿瘤复发率。我们的研究证实了这样一种理论，即灌注KLH会刺激细胞因子的产生，导致其在尿液中分泌。白细胞介素 - 1（IL - 1）通过多米诺效应刺激免疫级联反应，主要由活化的巨噬细胞产生。灌注方案在原发性浅表性细胞癌TUR术后5 - 7天开始。将20 mg KLH溶于20 ml 0.9%氯化钠溶液中，每周向膀胱内灌注1次，连续6周，然后每月灌注1次，持续1年。当将KLH灌注到膀胱中时，尿液中会分泌IL - 1α。使用特异性酶联免疫吸附测定（ELISA）进行分析。我们实验室建立的IL - 1α ELISA检测限为5 pg/ml。该IL - 1α ELISA在一系列测量中的偏差为3 - 7%，系列之间的偏差为5 - 15%。治疗组中IL - 1α分泌量在0至30,905 pg/24 h之间，对照组在0（收集期）至2,472 pg/4 h之间。膀胱癌患者灌注KLH后IL - 1α产量显著增加；然而，不同患者之间水平差异很大。在4 - 8小时内达到最大产量，24小时内下降。对照组和KLH组在24小时内产生的IL - 1α量存在显著差异。在接受KLH治疗的14例患者中，8例（57%）在接受KLH治疗6周后的尿液IL - 1α水平高于在12个月内无反应的患者，但这些水平无统计学意义。尿液中IL - 1α的分泌是膀胱对KLH抗原刺激的生物学反应。在尿液样本中未检测到IL - 2。尚有待确定是不存在IL - 2细胞因子，还是其含量低于ELISA所需的最低检测限。
