Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: Immunomodulation with IL-4R alpha antisense oligonucleotide prevents respiratory syncytial virus-mediated pulmonary disease.

Authors: Ripple, Michael J; You, Dahui; Honnegowda, Srinivasa; Giaimo, Joseph D; Sewell, Andrew B; Becnel, David M; Cormier, Stephania A

Published In J Immunol, (2010 Oct 15)

Abstract: Respiratory syncytial virus (RSV) causes significant morbidity and mortality in infants worldwide. Severe RSV infections in infants cause bronchiolitis, wheeze, and/or cough and significantly increase the risk for developing asthma. RSV pathogenesis is thought to be due to a Th2-type immune response initiated in response to RSV infection, specifically in the infant. Using a neonatal mouse system as an appropriate model for human infants, we sought to determine whether local inhibition of IL-4Rýý expression during primary RSV infection in the neonate would prevent Th2-skewed responses to secondary RSV infection and improve long-term pulmonary function. To reduce IL-4Rýý expression, antisense oligonucleotides (ASOs) specific for IL-4Rýý were administered intranasally to neonatal mice at the time of primary infection. Mice were initially infected with RSV at 1 wk of age and were reinfected at 6 wk of age. Administration of IL-4Rýý ASOs during primary RSV infection in neonatal mice abolished the pulmonary dysfunction normally observed following reinfection in the adult. This ablation of pulmonary dysfunction correlated with a persistent rebalancing of the Th cell compartment with decreased Th2 responses (i.e., reduced goblet cell hyperplasia, Th2 cells, and cytokine secretion) and increased Th1 responses (i.e., elevated Th1 cell numbers and type I Abs and cytokines). Our data support our hypothesis that a reduction in the Th2 immune response during primary infection in neonates prevents Th2-mediated pulmonary pathology initially and upon reinfection and further suggest that vaccine strategies incorporating IL-4Rýý ASOs may be of significant benefit to infants.

PubMed ID: 20861354 Exiting the NIEHS site

MeSH Terms: Animals; Animals, Newborn; Antibodies, Viral/blood; Dendritic Cells/immunology; Enzyme-Linked Immunosorbent Assay; Immunomodulation*; Lung Diseases/immunology; Lung Diseases/prevention & control*; Lung Diseases/virology; Mice; Mice, Inbred BALB C; Oligonucleotides, Antisense/pharmacology*; Receptors, Cell Surface/antagonists & inhibitors*; Respiratory Syncytial Virus Infections/immunology; Respiratory Syncytial Virus Infections/prevention & control*; Respiratory Syncytial Viruses/immunology; Th1 Cells/immunology; Th2 Cells/immunology; Viral Load

Back
to Top