Natural isoprenoids inhibit LPS-induced-production of cytokines and nitric oxide in aminobisphosphonate-treated monocytes

Annalisa Marcuzzi, Alberto Tommasini, Sergio Crovella, Alessandra Pontillo

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

The inhibition of mevalonate pathway through genetic defects (mevalonate kinase deficiency, MKD) or pharmacologic drugs (aminobisphosphonates) causes a shortage of intermediate compounds and, in particular, of geranylgeranyl-pyrophosphate (GGPP) associated to the activation of caspase-1 and IL-1β release. Geraniol (GOH), farnesol (FOH), geranylgeraniol (GGOH) and menthol (MOH), due to their isoprenoid structure, are supposed to enter the mevalonate pathway and to by-pass the biochemical block, reconstituting the pathway. Considering the already known side effects of aminobisphosphonates, and the lack of a specific treatment for MKD, we evaluated the impact of these natural isoprenoids compounds in a RAW cell lines chemically treated with the aminobisphosphonate alendronate, and in monocytes isolated from 2 patients affected by MKD. GOH, FOH, GGOH and MOH were all capable to diminish inflammatory marker levels induced by LPS. These natural isoprenoids could be proposed as novel therapeutic approach for the still orphan drug MKD, but also considered for the evaluation of possible inflammatory side effects of aminobisphosphonates.

Original languageEnglish
Pages (from-to)639-642
Number of pages4
JournalInternational Immunopharmacology
Volume10
Issue number6
DOIs
Publication statusPublished - Jun 2010

Fingerprint

Mevalonate Kinase Deficiency
Terpenes
Monocytes
Nitric Oxide
Cytokines
Mevalonic Acid
Orphan Drug Production
Farnesol
Menthol
Alendronate
Caspase 1
Interleukin-1
Cell Line
Therapeutics
Pharmaceutical Preparations

Keywords

  • Inflammation
  • Isoprenoid
  • MKD
  • Periodic fever

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Pharmacology

Cite this

Natural isoprenoids inhibit LPS-induced-production of cytokines and nitric oxide in aminobisphosphonate-treated monocytes. / Marcuzzi, Annalisa; Tommasini, Alberto; Crovella, Sergio; Pontillo, Alessandra.

In: International Immunopharmacology, Vol. 10, No. 6, 06.2010, p. 639-642.

Research output: Contribution to journalArticle

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