Perflubron reduces lung inflammation in respiratory syncytial virus infection by inhibiting chemokine expression and nuclear factor-κB activation

Helene A. Haeberle, Frances Nesti, Hans Juergen Dieterich, Zoran Gatalica, Roberto Garofalo

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Airway mucosa inflammation plays a critical role in the pathogenesis of lower respiratory tract infections caused by respiratory syncytial virus (RSV), the major etiologic agent of bronchiolitis in infancy. Type and intensity of cellular infiltration are dictated by inflammatory chemokines, which are rapidly and abundantly induced in lung tissue by RSV. This process is, to a large extent, transcriptionally regulated by RSV-mediated activation of the nuclear factor-κB. The administration of a perfluorocarbon (PFC) liquid, such as perflubron, during partial liquid ventilation improves lung function and also reduces inflammation. In this study we demonstrate that treatment of BALB/c mice with perflubron intranasally 6 hours after RSV infection significantly inhibited lung cellular inflammation as well as the expression of the chemokines RANTES, MIP-1α, MIP-1β, and MIP-2, compared with phosphate-buffered saline-treated control mice. However, perflubron treatment did not affect RSV replication. Strikingly, treatment with perflubron abrogated nuclear factor-κB activation in lung of RSV-infected mice. These results demonstrate a novel mechanism by which PFC may exert antiinflammatory activity and suggest that partial liquid ventilation with PFC may be considered in future clinical trials for infants with severe RSV infections requiring mechanical ventilation.

Original languageEnglish (US)
Pages (from-to)1433-1438
Number of pages6
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume165
Issue number10
DOIs
StatePublished - May 15 2002

Fingerprint

Respiratory Syncytial Virus Infections
Respiratory Syncytial Viruses
Chemokines
Pneumonia
Fluorocarbons
Liquid Ventilation
Lung
Inflammation
Virus Activation
Chemokine CCL5
Bronchiolitis
Virus Replication
Artificial Respiration
Respiratory Tract Infections
Mucous Membrane
Anti-Inflammatory Agents
Therapeutics
Phosphates
perflubron
Clinical Trials

Keywords

  • Chemokines
  • Inflammation
  • Nuclear factor-κB
  • Perflubron
  • Respiratory syncytial virus

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Perflubron reduces lung inflammation in respiratory syncytial virus infection by inhibiting chemokine expression and nuclear factor-κB activation. / Haeberle, Helene A.; Nesti, Frances; Dieterich, Hans Juergen; Gatalica, Zoran; Garofalo, Roberto.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 165, No. 10, 15.05.2002, p. 1433-1438.

Research output: Contribution to journalArticle

@article{84c684e735184d5d91b705d221537bb5,
title = "Perflubron reduces lung inflammation in respiratory syncytial virus infection by inhibiting chemokine expression and nuclear factor-κB activation",
abstract = "Airway mucosa inflammation plays a critical role in the pathogenesis of lower respiratory tract infections caused by respiratory syncytial virus (RSV), the major etiologic agent of bronchiolitis in infancy. Type and intensity of cellular infiltration are dictated by inflammatory chemokines, which are rapidly and abundantly induced in lung tissue by RSV. This process is, to a large extent, transcriptionally regulated by RSV-mediated activation of the nuclear factor-κB. The administration of a perfluorocarbon (PFC) liquid, such as perflubron, during partial liquid ventilation improves lung function and also reduces inflammation. In this study we demonstrate that treatment of BALB/c mice with perflubron intranasally 6 hours after RSV infection significantly inhibited lung cellular inflammation as well as the expression of the chemokines RANTES, MIP-1α, MIP-1β, and MIP-2, compared with phosphate-buffered saline-treated control mice. However, perflubron treatment did not affect RSV replication. Strikingly, treatment with perflubron abrogated nuclear factor-κB activation in lung of RSV-infected mice. These results demonstrate a novel mechanism by which PFC may exert antiinflammatory activity and suggest that partial liquid ventilation with PFC may be considered in future clinical trials for infants with severe RSV infections requiring mechanical ventilation.",
keywords = "Chemokines, Inflammation, Nuclear factor-κB, Perflubron, Respiratory syncytial virus",
author = "Haeberle, {Helene A.} and Frances Nesti and Dieterich, {Hans Juergen} and Zoran Gatalica and Roberto Garofalo",
year = "2002",
month = "5",
day = "15",
doi = "10.1164/rccm.2109077",
language = "English (US)",
volume = "165",
pages = "1433--1438",
journal = "American Journal of Respiratory and Critical Care Medicine",
issn = "1073-449X",
publisher = "American Thoracic Society",
number = "10",

}

TY - JOUR

T1 - Perflubron reduces lung inflammation in respiratory syncytial virus infection by inhibiting chemokine expression and nuclear factor-κB activation

AU - Haeberle, Helene A.

AU - Nesti, Frances

AU - Dieterich, Hans Juergen

AU - Gatalica, Zoran

AU - Garofalo, Roberto

PY - 2002/5/15

Y1 - 2002/5/15

N2 - Airway mucosa inflammation plays a critical role in the pathogenesis of lower respiratory tract infections caused by respiratory syncytial virus (RSV), the major etiologic agent of bronchiolitis in infancy. Type and intensity of cellular infiltration are dictated by inflammatory chemokines, which are rapidly and abundantly induced in lung tissue by RSV. This process is, to a large extent, transcriptionally regulated by RSV-mediated activation of the nuclear factor-κB. The administration of a perfluorocarbon (PFC) liquid, such as perflubron, during partial liquid ventilation improves lung function and also reduces inflammation. In this study we demonstrate that treatment of BALB/c mice with perflubron intranasally 6 hours after RSV infection significantly inhibited lung cellular inflammation as well as the expression of the chemokines RANTES, MIP-1α, MIP-1β, and MIP-2, compared with phosphate-buffered saline-treated control mice. However, perflubron treatment did not affect RSV replication. Strikingly, treatment with perflubron abrogated nuclear factor-κB activation in lung of RSV-infected mice. These results demonstrate a novel mechanism by which PFC may exert antiinflammatory activity and suggest that partial liquid ventilation with PFC may be considered in future clinical trials for infants with severe RSV infections requiring mechanical ventilation.

AB - Airway mucosa inflammation plays a critical role in the pathogenesis of lower respiratory tract infections caused by respiratory syncytial virus (RSV), the major etiologic agent of bronchiolitis in infancy. Type and intensity of cellular infiltration are dictated by inflammatory chemokines, which are rapidly and abundantly induced in lung tissue by RSV. This process is, to a large extent, transcriptionally regulated by RSV-mediated activation of the nuclear factor-κB. The administration of a perfluorocarbon (PFC) liquid, such as perflubron, during partial liquid ventilation improves lung function and also reduces inflammation. In this study we demonstrate that treatment of BALB/c mice with perflubron intranasally 6 hours after RSV infection significantly inhibited lung cellular inflammation as well as the expression of the chemokines RANTES, MIP-1α, MIP-1β, and MIP-2, compared with phosphate-buffered saline-treated control mice. However, perflubron treatment did not affect RSV replication. Strikingly, treatment with perflubron abrogated nuclear factor-κB activation in lung of RSV-infected mice. These results demonstrate a novel mechanism by which PFC may exert antiinflammatory activity and suggest that partial liquid ventilation with PFC may be considered in future clinical trials for infants with severe RSV infections requiring mechanical ventilation.

KW - Chemokines

KW - Inflammation

KW - Nuclear factor-κB

KW - Perflubron

KW - Respiratory syncytial virus

UR - http://www.scopus.com/inward/record.url?scp=0037092567&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037092567&partnerID=8YFLogxK

U2 - 10.1164/rccm.2109077

DO - 10.1164/rccm.2109077

M3 - Article

C2 - 12016108

AN - SCOPUS:0037092567

VL - 165

SP - 1433

EP - 1438

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

SN - 1073-449X

IS - 10

ER -