Vanderschueren B, Dumon J C, Oleffe V, Heymans C, Gérain J, Body J J
Bone Metabolism Unit, Institut Jules Bordet, Université Libre de Bruxelles, Belgium.
Cancer Immunol Immunother. 1994 Nov;39(5):286-90. doi: 10.1007/BF01519980.
Circulating interleukin-6 (IL-6) concentrations correlate with disease activity in severe inflammatory conditions, in sepsis and in some hematological malignancies. On the other hand, IL-6 is a potent stimulator of osteoclastogenesis and has been implicated as a contributory factor in the genesis of osteopenic conditions. We measured circulating IL-6 levels by a sensitive (detection limit of 10 U/ml) and specific bioassay in 103 patients with advanced cancer, including 41 with tumor-induced hypercalcemia before any specific hypocalcemic therapy. We related IL-6 concentrations to clinical features and to biochemical parameters of bone metabolism, including blood Ca, Ca2+, Pi, intact parathyroid hormone, parathyroid hormone-related protein, osteocalcin, 1,25-(OH)2-vitamin D and, as markers of bone resorption, the fasting urinary excretion of calcium (Ca/creatinine) and hydroxyproline. IL-6 levels were increased, i.e. detectable, in 23% of the patients, 8/41 (20%) hypercalcemic and 16/62 (26%) normocalcemic patients (NS); the distribution of the values was similar in the two groups. The presence of increased IL-6 concentrations was not related to any clinical characteristic, notably not to the survival nor to the existence of bone metastases, whether in hypercalcemic or normocalcemic patients; e.g., only 3/12 (25%) hypercalcemic subjects without bone metastases had elevated IL-6 levels. We found no significant correlations between IL-6 concentrations and any of the biochemical parameters studied. Hypercalcemic subjects with increased IL-6 had higher urinary Ca/creatinine levels than patients with normal IL-6 levels (P < 0.005) but this was not the case in normocalcemic subjects. Mean concentrations of inflammatory or other bone metabolism markers were not significantly different between patients with normal or with elevated IL-6 levels. In summary, circulating IL-6 levels were increased in 23% of 103 patients with advanced cancer, but the frequency of increased IL-6 concentrations was not related to the presence of hypercalcemia or to any marker of calcium metabolism or bone turnover. The pathogenic importance of circulating IL-6 in patients with solid tumors remains to be demonstrated and our data indicate that increased circulating levels of IL-6, possibly reflecting the activation of the immune system, only contribute in a minor way to the osteolytic process in patients with tumor-induced hypercalcemia.
循环白细胞介素-6（IL-6）浓度与严重炎症性疾病、脓毒症及某些血液系统恶性肿瘤的疾病活动相关。另一方面，IL-6是破骨细胞生成的强效刺激因子，被认为是骨质减少性疾病发生的一个促成因素。我们采用一种灵敏的（检测限为10 U/ml）特异性生物测定法，检测了103例晚期癌症患者的循环IL-6水平，其中41例在接受任何特异性降钙治疗前患有肿瘤诱导的高钙血症。我们将IL-6浓度与临床特征以及骨代谢的生化参数相关联，这些参数包括血钙、钙离子、无机磷、完整甲状旁腺激素、甲状旁腺激素相关蛋白、骨钙素、1,25-（OH）2-维生素D，以及作为骨吸收标志物的空腹尿钙（钙/肌酐）和羟脯氨酸。23%的患者IL-6水平升高，即可检测到，其中8/41（20%）高钙血症患者和16/62（26%）血钙正常患者（无显著性差异）；两组数值分布相似。IL-6浓度升高与任何临床特征均无关联，尤其是与高钙血症或血钙正常患者的生存率及骨转移的存在与否均无关；例如，仅有3/12（25%）无骨转移的高钙血症患者IL-6水平升高。我们发现IL-6浓度与所研究的任何生化参数之间均无显著相关性。IL-6升高的高钙血症患者的尿钙/肌酐水平高于IL-6水平正常的患者（P < 0.005），但血钙正常患者并非如此。IL-6水平正常或升高的患者之间，炎症或其他骨代谢标志物的平均浓度无显著差异。总之，103例晚期癌症患者中有23%的患者循环IL-6水平升高，但IL-6浓度升高的频率与高钙血症的存在或任何钙代谢或骨转换标志物均无关。循环IL-6在实体瘤患者中的致病重要性仍有待证实，我们的数据表明，循环IL-6水平升高可能反映了免疫系统的激活，但仅在肿瘤诱导的高钙血症患者的溶骨过程中起较小作用。
