Zileuton reduces respiratory illness and lung inflammation, during respiratory syncytial virus infection, in mice.
To determine the role of leukotrienes in a mouse model of respiratory syncytial virus (RSV) infection, we correlated the quantity of leukotrienes in lung lavage fluids of infected mice with respiratory rates and measures of outflow obstruction and then determined the effects of the leukotriene inhibitor zileuton on clinical features and lung function. Concentrations of leukotrienes were correlated with both increasing respiratory rates and the degree of prolongation of expiratory time. Administration of zileuton 1 day before infection and through day 5 after infection markedly reversed airway constriction, reduced numbers of inflammatory cells in the lung, and prevented the weight loss associated with infection. Leukotrienes appear to contribute substantially to the pathogenesis of RSV-related disease.
Welliver
R Charles
RC
Department of Pediatrics, Division of Infectious Diseases, State University of New York at Buffalo, and Children's Hospital, Buffalo, New York 14222, USA. twelliver@upa.chob.edu
Hintz
Karen H
KH
Glori
Maria
M
Welliver
Robert C
RC
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D004195:Disease Models, Animal; D006918:Hydroxyurea / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D020024:Leukotriene Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015289:Leukotrienes / Q000032:analysis / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy* / Q000473:pathology* / Q000517:prevention & control; D012136:Respiratory Syncytial Viruses / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects; D015431:Weight Loss / Q000187:drug effects
D020024:Leukotriene Antagonists; D015289:Leukotrienes; C063449:zileuton; D006918:Hydroxyurea