Weisinger J R, Alonzo E, Bellorín-Font E, Blasini A M, Rodriguez M A, Paz-Martínez V, Martinis R
Division of Nephrology, and Rheumatology, Hospital Universitario de Caracas, Venezuela.
Kidney Int. 1996 Jan;49(1):244-50. doi: 10.1038/ki.1996.34.
Decreased bone mass has been reported in patients with idiopathic hypercalciuria. Previous studies, using bioassays, have suggested a role of interleukin-1 (IL-1), in the decreased bone mineral density (BMD) of fasting hypercalciuria. The present study was designed to determine which IL-1 fraction (alpha or beta) correlates with bone resorption and whether other known bone resorting cytokines like interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) may play a role in this process. Cytokines production was determined by quantitative and specific analysis, enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase polymerase chain reaction (RT-PCR). Dual-energy X-ray absorptiometry and cytokine production by unstimulated and lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) were determined in a group of 29 patients with recurrent nephrolithiasis (17 hypercalciurics and 12 normocalciurics), and 12 healthy controls. The hypercalciuric subjects showed lower vertebral BMD than the normocalciuric or normal controls. There was no difference in spinal or femoral BMD between absorptive or fasting hypercalciurics. A significant negative correlation existed between urinary calcium excretion and vertebral BMD (r = -0.55, P < 0.01). Basal IL-1 alpha production correlated with vertebral BMD (r = -0.45, P < 0.02). This correlation was not seen with IL-1 beta, IL-6 or TNF-alpha production. LPS-induced IL-6 and TNF-alpha production were enhanced in the hypercalciuric patients, when compared to normocalciurics or controls. Control and normocalciuric subjects showed minimal amounts of IL-1 alpha mRNA. In contrast, hypercalciuric patients showed a significant increase of spontaneous IL-1 alpha mRNA transcription. These results suggest that different cytokines could be involved in the bone resorption process observed in hypercalciuria.
据报道，特发性高钙尿症患者存在骨量减少的情况。以往使用生物测定法的研究表明，白细胞介素-1（IL-1）在空腹高钙尿症患者骨矿物质密度（BMD）降低中发挥作用。本研究旨在确定哪种IL-1组分（α或β）与骨吸收相关，以及其他已知的骨吸收细胞因子如白细胞介素-6（IL-6）和肿瘤坏死因子α（TNF-α）是否在此过程中发挥作用。通过定量和特异性分析、酶联免疫吸附测定（ELISA）和逆转录聚合酶链反应（RT-PCR）来测定细胞因子的产生。对29例复发性肾结石患者（17例高钙尿症患者和12例正常钙尿症患者）以及12名健康对照者进行双能X线吸收测定，并测定未刺激和脂多糖（LPS）刺激的外周血单核细胞（PBMC）产生的细胞因子。高钙尿症患者的椎体BMD低于正常钙尿症患者或正常对照者。吸收性或空腹高钙尿症患者的脊柱或股骨BMD无差异。尿钙排泄与椎体BMD之间存在显著负相关（r = -0.55，P < 0.01）。基础IL-1α产生与椎体BMD相关（r = -0.45，P < 0.02）。IL-1β、IL-6或TNF-α产生与椎体BMD之间未观察到这种相关性。与正常钙尿症患者或对照者相比，高钙尿症患者LPS诱导的IL-6和TNF-α产生增强。对照者和正常钙尿症患者显示出少量的IL-1α mRNA。相反，高钙尿症患者的自发IL-1α mRNA转录显著增加。这些结果表明，不同的细胞因子可能参与了高钙尿症中观察到的骨吸收过程。
