Leukotriene pathway in sickle cell disease: A potential target for directed therapy

Jessica Knight-Perry, Michael R. Debaun, Robert C. Strunk, Joshua J. Field

Research output: Contribution to journalReview articlepeer-review

16 Scopus citations

Abstract

Sickle cell disease (SCD) is characterized by recurrent episodes of vaso-occlusion, resulting in tissue ischemia and end-organ damage. Inflammation is critical to the pathogenesis of vaso-occlusion and has been associated with SCD-related morbidity and mortality. Despite the impact of inflammation, no directed anti-inflammatory therapies for the treatment or prevention of vaso-occlusive events currently exist. Among individuals with SCD, asthma is a comorbid inflammatory condition that increases the risk of pain episodes, acute chest syndrome and death. Inflammation associated with asthma could augment the proinflammatory state of SCD, increasing episodes of vaso-occlusion. Leukotrienes are inflammatory mediators that play a prominent role in the pathogenesis of asthma and have been associated with SCD-related morbidity. Targeting inflammatory mediators, such as leukotrienes, is a promising approach for the development of novel therapies for the treatment of SCD. This review will examine the relationship between inflammation and vaso-occlusion, with particular focus on the leukotriene pathway.

Original languageEnglish (US)
Pages (from-to)57-68
Number of pages12
JournalExpert Review of Hematology
Volume2
Issue number1
DOIs
StatePublished - 2009

Bibliographical note

Funding Information:
J Field has received support from the National Heart, Lung and Blood Institute grant K12-HL08710, and J Knight-Perry has received support from the Doris Duke Charitable Foundation grant 2004061. JJ Field is the primary investigator for a site involved in a Phase II clinical trial sponsored by TRF Pharma, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Keywords

  • Asthma
  • Inflammation
  • Leukotriene
  • Sickle cell disease
  • Vaso-occlusion

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