Journal article
Intratracheal double-stranded RNA plus interferon-gamma: a model for analysis of the acute phase response to respiratory viral infections
Life sciences (1973), Vol.74(20), pp.2563-2576
04/02/2004
Handle:
https://hdl.handle.net/2376/114536
PMID: 15010266
Abstract
Double-stranded (ds)RNA is made as a by-product of viral replication. Synthetic dsRNA induces virtually all of the same systemic symptoms as acute viral infections, such as fever and malaise. In order to develop a model of respiratory viral infections (such as influenza) suitable for use in gene knockout mice (where the deleted gene may affect viral replication), we examined C57BL/6 mouse body temperature and locomotor activity responses to the synthetic dsRNA polyriboinosinic.polyribocytidylic acid (poly[rI.rC]) introduced via the intratracheal (IT) route. We compared the IT poly[rI.rC] responses to the well-characterized intraperitoneal (IP) poly[rI.rC] responses. IT poly[rI.rC] failed to induce an acute phase response (APR) in mice, in contrast to IP poly[rI.rC]. However, addition of interferon (IFN)gamma to the IT poly[rI.rC] inoculum induced sustained hypothermia and suppressed locomotor activity responses with similar kinetics to those responses seen in acute mouse influenza. We further examined cytokine, antiviral, muscarinic M2 receptor and inducible nitric oxide synthase gene expression at 5 hr in the lungs of IT challenged mice. These studies suggested that priming the lung with IFNgamma could enhance proinflammatory (IL1beta, IL6, TNFalpha) cytokine gene expression and suppress interferon gene expression compared to IT poly[rI.rC] alone. No differences were detected for the other genes examined. While further molecular characterization of the model is required, we demonstrate that IT challenge with combined poly[rI.rC] and IFNgamma closely simulates the APR to an acute respiratory virus, and may serve as a suitable model for analyzing the molecular basis of the viral APR in gene knockout mice.
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Details
- Title
- Intratracheal double-stranded RNA plus interferon-gamma: a model for analysis of the acute phase response to respiratory viral infections
- Creators
- Tim R Traynor - Department of VCAPP, College of Veterinary Medicine, Washington State University, PO Box 646520, Pullman, WA 99164-6520, USAJeannine A MajdeStewart G BohnetJames M Krueger
- Publication Details
- Life sciences (1973), Vol.74(20), pp.2563-2576
- Academic Unit
- Integrative Physiology and Neuroscience, Department of
- Publisher
- Netherlands
- Grant note
- HD 36520 / NICHD NIH HHS NS 25378 / NINDS NIH HHS
- Identifiers
- 99900547792101842
- Language
- English
- Resource Type
- Journal article