Abstract |
Respiratory syncytial virus (RSV) is an important cause of viral respiratory disease in children, and RSV bronchiolitis has been associated with the development of asthma in childhood. RSV spreads from the eye and nose to the human respiratory tract. Correlative studies of humans and direct infection studies of BALB/c mice have established the eye as a significant pathway of entry of RSV to the lung. At the same time, RSV infection of the eye produces symptoms resembling allergic conjunctivitis. Cysteinyl leukotrienes (CysLTs) are known promoters of allergy and inflammation, and the first step in their biogenesis from arachidonic acid is catalyzed by 5-lipoxygenase (5-LO) in concert with the 5-LO-activating protein (FLAP). We have recently developed a novel compound, AM679, which is a topically applied and potent inhibitor of FLAP. Here we show with the BALB/c mouse eye RSV infection model that AM679 markedly reduced the RSV-driven ocular pathology as well as the synthesis of CysLTs in the eye. In addition, AM679 decreased the production of the Th2 cell cytokine interleukin-4 but did not increase the viral load in the eye or the lung. These results suggest that FLAP inhibitors may be therapeutic for RSV-driven eye disease and possibly other inflammatory eye indications.
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Authors | Alla Musiyenko, Lucia Correa, Nicholas Stock, John H Hutchinson, Daniel S Lorrain, Gretchen Bain, Jilly F Evans, Sailen Barik |
Journal | Clinical and vaccine immunology : CVI
(Clin Vaccine Immunol)
Vol. 16
Issue 11
Pg. 1654-9
(Nov 2009)
ISSN: 1556-679X [Electronic] United States |
PMID | 19759251
(Publication Type: Journal Article)
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Chemical References |
- 5-Lipoxygenase-Activating Proteins
- ALOX5AP protein, human
- Alox5ap protein, mouse
- Carrier Proteins
- Enzyme Inhibitors
- Immunologic Factors
- Membrane Proteins
- Interleukin-4
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Topics |
- 5-Lipoxygenase-Activating Proteins
- Animals
- Carrier Proteins
(antagonists & inhibitors)
- Enzyme Inhibitors
(therapeutic use)
- Eye
(virology)
- Eye Diseases
(drug therapy, immunology, pathology)
- Female
- Immunologic Factors
(therapeutic use)
- Inflammation
(pathology, prevention & control)
- Interleukin-4
(biosynthesis)
- Lung
(virology)
- Membrane Proteins
(antagonists & inhibitors)
- Mice
- Mice, Inbred BALB C
- Respiratory Syncytial Virus Infections
(drug therapy, immunology, pathology)
- Respiratory Syncytial Viruses
(immunology)
- Viral Load
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