Pathophysiological role of IL-6 and IL-8 in the progression of prostate cancer and cachexia

在体外实验中，前列腺癌细胞系PC3、DU145、JCA1产生IL-6。IL-6能促进PCS细胞的生长。抗IL-6抗体的存在抑制了JCA1细胞的生长。这些结果表明IL-6是由前列腺癌细胞产生并调节前列腺癌细胞的生长。血清IL-6与前列腺癌临床分期有显著相关性。肿瘤组织学与血清IL-6无显著相关性。血清IL-6水平【大于或等于】7 pg/ml的患者血清PSA、LDH、ALP水平显著高于血清IL-6水平< 7 pg/ml的患者。在EOD和血清IL-6之间发现了显著的关联。血清IL-6【大于或等于】7 pg/ml的患者生存率明显低于血清IL-6 < 7 pg/ml的患者。多因素Cox比例风险模型分析显示，EOD和IL-6是影响预后的重要因素。这些结果表明，血清IL-6水平与疾病侵袭性有关，是前列腺癌的一个重要预后因素。与未治疗患者和缓解患者相比，复发患者的血清TNF活性升高。血清TNF水平升高的患者血清总蛋白和白蛋白水平、血红蛋白水平和体重指数明显低于血清TNF水平未检测到的患者。血清白蛋白水平< 3.5 g/dl、血红蛋白水平< 11.0 g/dl、体重指数< 21 kg/m2的患者血清TNF水平显著高于相应组。血清TNF水平升高的患者的死亡率明显高于血清TNF水平未检测到的患者。这些发现提示TNF可能是导致前列腺癌患者恶病质复杂综合征的因素之一。

In in vitro experiments, prostate cancer cell lines, PC3, DU145, JCA1 produced IL-6. The growth of PCS cells was enhanced by IL-6. The growth of JCA1 cells was inhibited in the presence of anti IL-6 antibody. These results suggest that IL-6 is produced by prostate cancer cells and regulate the growth of prosate cancer cells. Serum IL-6 was significantly correlated with the clinical stage of prostate cancer. There was no significant association between tumor histology and serum IL-6. The serum PSA, LDH and ALP levels in the patients with serum IL-6 levels 【greater than or equal】 7 pg/ml were significantly higher than those in patients with serum IL-6 levels < 7 pg/ml. A significant association was found between EOD and serum IL-6. Patients with serum IL-6 【greater than or equal】 7 pg/ml had a significantly lower survival rate than those with serum IL-6 < 7 pg/ml. Multivariate Cox's proportional hazards model analysis showed that the significant prognostic factors were EOD and IL-6. These results indicate that the serum IL-6 level is asoociate with disease aggressiveness and a significant prognostic factor for prostate cancer. Serum TNF activity was elevated in patients with relapsed disease, when compared with the untreated patients and patients in remission. The serum total protein and albumin levels, hemoglobin levels, and body mass index of the patients with elevated serum TNF levels were significantly lower than those in patients with undetectable serum TNF levels. The serum TNF levels of patients with serum albumin levels of < 3.5 g/dl, hemoglobin levels of < 11.0 g/dl and a body mass index of < 21 kg/m2 were significantly higher than the values in their respective counterparts. Patients with elevated serum TNF levels had a significantly higher mortality rate than those with undetectable serum TNF levels. These findings suggest that TNF may be one of the factors contributing to the complex syndrome of cachexia in patients with prostate cancer.