Drachenberg D E, Elgamal A A, Rowbotham R, Peterson M, Murphy G P
Pacific Northwest Cancer Foundation/Northwest Hospital, Seattle, Washington.
Prostate. 1999 Oct 1;41(2):127-33. doi: 10.1002/(sici)1097-0045(19991001)41:2<127::aid-pros7>3.0.co;2-h.
Interleukin-6 (IL-6) is a cytokine that plays a central role in host defense due to its wide range of immune and hematopoietic activities. It is found in high levels in human ejaculate, and has recently been found to regulate prostate-specific protein expression in prostate cancer cells through nonsteroidal activation of the androgen receptor. IL-6 may be a candidate mediator of morbidity in patients with metastatic disease. We attempted to evaluate the potential of circulating IL-6 levels as a marker of disease progression. MATERIALS AND METHODS Serum IL-6, prostate specific antigen (PSA), percent free PSA (%fPSA), and prostate-specific membrane antigen (PSMA) were measured using commercially available assays in 407 men, including 15 controls. The rest of the study population had clinical or histologic evidence of prostate diseases, including 41 patients with chronic prostatitis, 167 with benign prostatic hyperplasia (BPH), 8 with high-grade prostatic intraepithelial neoplasia (PIN), 88 with localized prostate cancer, 22 with local recurrence after treatment of primary tumor, 4 with advanced untreated disease (nodal or bony metastases), 23 with advanced hormone dependent disease, and 39 with advanced hormone refractory disease (PSA > 1.0 ng/ml while on hormone treatment and/or evidence of disease progression). None had history of concurrent malignancy or acute inflammatory condition. Kruskal-Wallis analysis of variance and Spearman's correlation analysis were used for statistical analyses.
Serum levels of IL-6 were significantly elevated in patients with clinically evident hormone refractory disease (5.7 +/- 1.9 pg/ml) and statistical significance was seen when comparing the elevated serum IL-6 levels to those in normal controls, prostatitis, BPH, and localized and recurrent disease, (P values < 0.01). Compared to serum levels of controls and BPH, PSA was significantly elevated in advanced untreated disease and hormone refractory groups (P < 0.05). Percent fPSA was significantly lower in all cancer patients but the hormone refractory. Serum PSMA was elevated in advanced untreated prostate cancer. Serum IL-6 showed positive correlation with PSMA and negative correlation with serum PSA but did not attain statistical significance.
Serum IL-6 levels are significantly elevated in hormone-refractory prostate cancer patients and may be a surrogate marker of the androgen independent phenotype.
白细胞介素-6（IL-6）是一种细胞因子，因其广泛的免疫和造血活性，在宿主防御中发挥核心作用。它在人类精液中含量很高，最近发现它通过雄激素受体的非甾体激活来调节前列腺癌细胞中前列腺特异性蛋白的表达。IL-6可能是转移性疾病患者发病的候选介质。我们试图评估循环IL-6水平作为疾病进展标志物的潜力。
使用市售检测方法对407名男性进行血清IL-6、前列腺特异性抗原（PSA）、游离PSA百分比（%fPSA）和前列腺特异性膜抗原（PSMA）检测，其中包括15名对照者。其余研究人群有前列腺疾病的临床或组织学证据，包括41例慢性前列腺炎患者、167例良性前列腺增生（BPH）患者、8例高级别前列腺上皮内瘤变（PIN）患者、88例局限性前列腺癌患者、22例原发性肿瘤治疗后局部复发患者、4例晚期未治疗疾病（淋巴结或骨转移）患者、23例晚期激素依赖性疾病患者和39例晚期激素难治性疾病患者（激素治疗期间PSA>1.0 ng/ml和/或有疾病进展证据）。所有患者均无并发恶性肿瘤或急性炎症病史。采用Kruskal-Wallis方差分析和Spearman相关分析进行统计分析。
临床明显的激素难治性疾病患者血清IL-6水平显著升高（5.7±1.9 pg/ml），与正常对照、前列腺炎、BPH以及局限性和复发性疾病患者的血清IL-6水平相比具有统计学意义（P值<0.01）。与对照组和BPH组的血清水平相比，晚期未治疗疾病组和激素难治性疾病组的PSA显著升高（P<0.05）。除激素难治性患者外，所有癌症患者的%fPSA均显著降低。晚期未治疗的前列腺癌患者血清PSMA升高。血清IL-6与PSMA呈正相关，与血清PSA呈负相关，但未达到统计学意义。
激素难治性前列腺癌患者血清IL-6水平显著升高，可能是雄激素非依赖表型的替代标志物。
