Leukotrienes play protective roles early during experimental VSV encephalitis

Nannan Chen, Andrew Restivo, Carol Shoshkes Reiss

Research output: Contribution to journalArticlepeer-review

Abstract

Leukotrienes (LT) are potent lipid mediators of inflammation. 5-Lipoxygenase (5-LO) is the key enzyme in the conversion of arachidonic acid to LT. There are four LT: LTB4, LTC4, LTD4 and LTE4. LT have been extensively studied in airway inflammation but little is known about their roles in viral infection in the CNS. LTB4 is a chemoattractant for neutrophils. In this work, we studied the roles of LT in acute vesicular stomatitis virus (VSV) encephalitis. Two methods were used to disrupt 5-LO activity: mice were treated with Zileuton™, an enzyme antagonist, or 5-LO genetic knockout mice were used. We found that inhibition or deletion of 5-LO resulted in: (a) impaired process of neutrophil infiltration into the CNS early during viral infection; (b) fewer neurons expressed nitric oxide synthase-1 (NOS-1); (c) higher viral titers 1 day after viral infection; and (d) increased disruption of blood brain barrier (BBB). Our studies suggest that LT are important innate immune players during VSV pathogenesis and are beneficial to the host in early control of viral replication in the CNS.

Original languageEnglish (US)
Pages (from-to)94-102
Number of pages9
JournalJournal of Neuroimmunology
Volume120
Issue number1-2
DOIs
StatePublished - 2001

Keywords

  • In vivo animal models
  • Inflammatory mediators
  • Neuroimmunology
  • Neutrophils

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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