Leukotrienes play protective roles early during experimental VSV encephalitis

Leukotrienes (LT) are potent lipid mediators of inflammation. 5-Lipoxygenas e (5-LO) is the key enzyme in the conversion of arachidonic acid to LT. The re 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 infe ction in the CNS. LTB4 is a chemoattractant for neutrophils. In this work, we studied the roles of LT in acute vesicular stomatitis virus (VSV) enceph alitis. Two methods were used to disrupt 5-LO activity: mice were treated w ith Zileuton (TM), an enzyme antagonist, or 5-LO genetic knockout mice were used. We found that inhibition or deletion of 5-LO resulted in: (a) impair ed process of neutrophil infiltration into the CNS early during viral infec tion; (b) fewer neurons expressed nitric oxide synthase-1 (NOS-1); (c) high er viral titers I day after viral infection; and (d) increased disruption o f blood brain barrier (BBB). Our studies suggest that LT are important inna te immune players during VSV pathogenesis and are beneficial to the host in early control of viral replication in the CNS. (C) 2001 Elsevier Science B .V. All rights reserved.