Institute for Maternal and Child Health-IRCCS Burlo Garofolo, via dell'Istria 65/1, 34137 Trieste, Italy.
Inflamm Res. 2012 Dec;61(12):1363-7. doi: 10.1007/s00011-012-0537-4. Epub 2012 Aug 1.
A potential anti-inflammatory effect of clodronate--an aminobisphosphonate--was described to antagonize the pro-inflammatory effects of the block in the mevalonate pathway, the main feature of a rare auto-inflammatory disease called mevalonate kinase deficiency (MKD).
In this study we evaluated the potential anti-inflammatory effect of clodronate in MKD--a still orphan drug pediatric disease.
We studied some biological parameters, nitric oxide production using Griess reagents and programmed cell death by flow cytometry, as common inflammatory parameters in MKD, in the presence of different doses of clodronate (1, 10 and 100 μM).
In our cellular model and in monocytes from patients with MKD, clodronate induced an increase in programed cell death and nitric oxide production in comparison with non-treated cells.
Our findings suggest that clodronate does not have an anti-inflammatory effect as previously reported but that it increases the epiphenomena of this pediatric disease.
氯膦酸二钠是一种氨基双膦酸盐，具有潜在的抗炎作用，能够拮抗法呢醇通路阻断所产生的促炎作用，而法呢醇通路阻断是一种罕见的自身炎症性疾病——甲羟戊酸激酶缺乏症（MKD）的主要特征。
本研究评估了氯膦酸二钠在 MKD（一种仍处于孤儿药研发阶段的儿科疾病）中的潜在抗炎作用。
我们研究了一些生物学参数，如使用格里试剂检测一氧化氮的产生和流式细胞术检测程序性细胞死亡，作为 MKD 的常见炎症参数，同时观察了不同浓度的氯膦酸二钠（1、10 和 100 μM）的作用。
在我们的细胞模型和 MKD 患者的单核细胞中，与未处理的细胞相比，氯膦酸二钠诱导了程序性细胞死亡和一氧化氮产生的增加。
我们的研究结果表明，氯膦酸二钠并没有如先前报道的那样具有抗炎作用，反而增加了这种儿科疾病的继发表现。
