Journal article
Oseltamivir Treatment Prevents the Increased Influenza Virus Disease Severity and Lethality Occurring in Chronic Ethanol Consuming Mice
Alcoholism, clinical and experimental research, Vol.34(8), pp.1425-1431
2010
DOI: 10.1111/j.1530-0277.2010.01226.x
PMCID: PMC2910177
PMID: 20497135
Abstract
Background: Chronic consumption of ethanol (EtOH) is well recognized to lead to defective innate and adaptive immune responses and increase the severity of pulmonary infections. Our own studies have demonstrated that chronic EtOH consumption decreases CD8 T-cell immunity to influenza virus infections (IAV) leading to severe infections and mortality. Interestingly, antiviral treatment of IAVs has been shown to be compromised in mice and humans that are immuno-deficient. It is known that EtOH can alter the pharmacokinetics of antivirals. Therefore, the effectiveness of influenza antiviral therapy during chronic ethanol consumption remains in question.
Methods: BALB/c mice were placed on 18% (w/v) EtOH in their drinking water for 8 weeks. Chronic EtOH consuming and water controls were then treated with 10 mg/kg oseltamivir orally and infected intranasally with influenza virus 4 hours post-oseltamivir treatment. The mice were then treated with oseltamivir twice daily until day 7 postinfection. Influenza disease severity was measured by morbidity and mortality, pulmonary viral titers, and histology.
Results: Chronic EtOH consuming mice infected with IAV and treated with oseltamivir have decreased morbidity and mortality, pulmonary viral titers, and pulmonary pathology compared to untreated EtOH mice.
Conclusions: Despite the severe immune defect seen in chronic EtOH mice as well as the potential for EtOH to inhibit the conversion of oseltamivir into an active form, treatment with oseltamivir reduces viral shedding as well as disease severity. These data suggest that the combination of a limited adaptive immune response plus the anti-IAV drug oseltamivir is sufficient to curb high mortality and mediate resolution of IAVs in mice chronically consuming ethanol.
Details
- Title: Subtitle
- Oseltamivir Treatment Prevents the Increased Influenza Virus Disease Severity and Lethality Occurring in Chronic Ethanol Consuming Mice
- Creators
- Ryan A LANGLOIS - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, United StatesDavid K MEYERHOLZ - Department of Pathology, University of Iowa, Iowa City, Iowa, United StatesRuth A COLEMAN - Department of Pathology, University of Iowa, Iowa City, Iowa, United StatesRobert T COOK - Department of Pathology, University of Iowa, Iowa City, Iowa, United StatesThomas J WALDSCHMIDT - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, United StatesKevin L LEGGE - Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, Iowa, United States
- Resource Type
- Journal article
- Publication Details
- Alcoholism, clinical and experimental research, Vol.34(8), pp.1425-1431
- Publisher
- Wiley; Hoboken, NJ
- DOI
- 10.1111/j.1530-0277.2010.01226.x
- PMID
- 20497135
- PMCID
- PMC2910177
- ISSN
- 0145-6008
- eISSN
- 1530-0277
- Language
- English
- Date published
- 2010
- Academic Unit
- Microbiology and Immunology; Pathology
- Record Identifier
- 9984047759602771
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