The effect of clodronate on a mevalonate kinase deficiency cellular model

V Zanin, A Marcuzzi, E Piscianz, J Vuch… - Inflammation …, 2012 - Springer
Inflammation Research, 2012Springer
Background 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). Objective In this study we evaluated the potential anti-inflammatory effect
of clodronate in MKD—a still orphan drug pediatric disease. Methods We studied some
biological parameters, nitric oxide production using Griess reagents and programmed cell …
Background
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).
Objective
In this study we evaluated the potential anti-inflammatory effect of clodronate in MKD—a still orphan drug pediatric disease.
Methods
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).
Results
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.
Conclusion
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.
Springer
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