Pharmacological modulators of sphingolipid metabolism for the treatment of cystic fibrosis lung inflammation

Strategies aimed to limit the excessive inflammatory response by targeting neutrophil recruitment are a relevant approach for CF patients. In general, each anti-inflammatory molecule should balance between the anti-infective role of neutrophils and the detrimental effects that they produce in the course of chronic inflammation due to the release of proteases and reactive oxygen species. In this respect, while others anti-inflammatory based therapies have failed in humans with CF in the past, the regulation of SLs may represent a useful potential target for pharmacotherapy. This review summarizes evidence derived from the validation of the anti-inflammatory properties of miglustat in bronchial epithelial cells in vitro and in murine models of lung inflammation and infection in vivo, demonstrating a down-regulation of neutrophils chemotactic signaling. Recalling that miglustat is an orally bioavailable FDA-approved and EMA−designated orphan available drug, therapeutic trials for CF patients could be envisioned in the near future.