Ribavirin and cysteinyl leukotriene-1 receptor blockade as treatment for severe bronchiolitis

Department of Pediatrics, State University of New York Upstate Medical University, Syracuse, New York, United States
Antiviral Research (Impact Factor: 3.94). 03/2006; 69(2):53-9. DOI: 10.1016/j.antiviral.2005.10.004
Source: PubMed

ABSTRACT In this work we have evaluated the clinical responses of pneumovirus-infected mice to combination therapy with the antiviral agent, ribavirin, and the CysLT1 cysteinyl leukotriene receptor antagonist, montelukast. We observed substantial virus replication in our mouse model of pneumovirus infection and significant accumulation of cysteinyl leukotrienes in lung tissue, the latter detected at levels that correlate directly with granulocyte recruitment to the airways. While administration of the nucleoside analog, ribavirin, reduced virus replication approximately 2,000-fold, the clinical outcomes as measured by morbidity and mortality, in response to ribavirin monotherapy were indistinguishable from those of the no-treatment controls. Similarly, montelukast therapy alone did not reduce granulocyte recruitment nor did it improve the clinical outcome. However, combined therapy with ribavirin and montelukast resulted in a significant reduction in morbidity and a substantial reduction in mortality (50% survival at t = 14 days and onward, compared to 10-20% survival in response to montelukast alone or to ribavirin alone, respectively, p < 0.01). These findings define further the independent contributions made by virus replication and by the ensuing inflammatory response to the detrimental sequelae of pneumovirus infection in vivo.

Download full-text


Available from: Cynthia Bonville, Jul 16, 2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: Image smoothing is a useful and necessary part of image processing. Both the median and mean filters are popular smoothing methods, but there can be problems when these two filters are applied to an image corrupted by unknown noise. We present a spatial domain probability filter which achieves the advantages of median and mean filters. The aim of our probability filter is to provide a compromise between the two more conventional filters. We present experimental results and performance evaluation of the median, mean filters and this probability filter operating on an image corrupted by impulse-like or random noise
    Intelligence and Systems, 1998. Proceedings., IEEE International Joint Symposia on; 06/1998
  • Perspectives in Medical Virology 01/2006; 14:299-320. DOI:10.1016/S0168-7069(06)14010-0
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pneumonia virus of mice (PVM; family Paramyxoviridae, genus Pneumovirus) is a natural mouse pathogen that is closely related to human and bovine respiratory syncytial viruses. Among the prominent features of this infection, robust replication of PVM takes place in bronchial epithelial cells in response to a minimal virus inoculum. Virus replication in situ results in local production of proinflammatory cytokines (MIP-1alpha, MIP-2, MCP-1 and IFNgamma) and granulocyte recruitment to the lung. If left unchecked, PVM infection and the ensuing inflammatory response ultimately lead to pulmonary edema, respiratory compromise and death. In this review, we consider the recent studies using the PVM model that have provided important insights into the role of the inflammatory response in the pathogenesis of severe respiratory virus infection. We also highlight several works that have elucidated acquired immune responses to this pathogen, including T cell responses and the development of humoral immunity. Finally, we consider several immunomodulatory strategies that have been used successfully to reduce morbidity and mortality when administered to PVM-infected, symptomatic mice, and thus hold promise as realistic therapeutic strategies for severe respiratory virus infections in human subjects.
    Immunology Letters 07/2008; 118(1):6-12. DOI:10.1016/j.imlet.2008.03.013 · 2.37 Impact Factor
Show more