TY - JOUR
T1 - Anti-Respiratory Syncytial Virus (RSV) Neutralizing Antibody Decreases Lung Inflammation, Airway Obstruction, and Airway Hyperresponsiveness in a Murine RSV Model
AU - Mejías, Asunción
AU - Chávez-Bueno, Susana
AU - Ríos, Ana María
AU - Saavedra-Lozano, Jesús
AU - Aten, Mónica Fonseca
AU - Hatfield, Jeanine
AU - Kapur, Payal
AU - Gómez, Ana María
AU - Jafri, Hasan S.
AU - Ramilo, Octavio
PY - 2004/5
Y1 - 2004/5
N2 - Numerous studies have described a strong association between respiratory syncytial virus (RSV) infection in infancy and the development of recurrent wheezing and airway hyperresponsiveness. We evaluated the effect of an anti-RSV neutralizing monoclonal antibody (palivizumab) on different aspects of RSV disease by using a murine model. BALB/c mice were intranasally inoculated with RSV A2. Palivizumab or an isotype-matched control antibody was administered once at 24 h before inoculation, 1 h after inoculation, or 48 h after inoculation. Regardless of the timing of administration, all mice treated with the neutralizing antibody showed significantly decreased RSV loads in bronchoalveolar lavage (BAL) and lung specimens compared with those of infected controls. Pulmonary histopathologic scores, airway obstruction measured by plethysmography, and airway hyperresponsiveness after methacholine challenge were significantly reduced in mice treated with the anti-RSV antibody 24 h before inoculation compared with those for untreated controls. Concentrations of interferon-gamma, interleukin-10, macrophage inflammatory protein 1α, regulated on activation normal T-cell expressed and secreted (RANTES), and eotaxin in BAL fluids were also significantly reduced in mice treated with palivizumab 24 h before inoculation. This study demonstrates that reduced RSV replication was associated with significant modulation of inflammatory and clinical markers of acute disease severity and significant improvement of the long-term pulmonary abnormalities. Studies to determine whether strategies aimed at preventing or reducing RSV replication could decrease the long-term morbidity associated with RSV infection in children should be considered.
AB - Numerous studies have described a strong association between respiratory syncytial virus (RSV) infection in infancy and the development of recurrent wheezing and airway hyperresponsiveness. We evaluated the effect of an anti-RSV neutralizing monoclonal antibody (palivizumab) on different aspects of RSV disease by using a murine model. BALB/c mice were intranasally inoculated with RSV A2. Palivizumab or an isotype-matched control antibody was administered once at 24 h before inoculation, 1 h after inoculation, or 48 h after inoculation. Regardless of the timing of administration, all mice treated with the neutralizing antibody showed significantly decreased RSV loads in bronchoalveolar lavage (BAL) and lung specimens compared with those of infected controls. Pulmonary histopathologic scores, airway obstruction measured by plethysmography, and airway hyperresponsiveness after methacholine challenge were significantly reduced in mice treated with the anti-RSV antibody 24 h before inoculation compared with those for untreated controls. Concentrations of interferon-gamma, interleukin-10, macrophage inflammatory protein 1α, regulated on activation normal T-cell expressed and secreted (RANTES), and eotaxin in BAL fluids were also significantly reduced in mice treated with palivizumab 24 h before inoculation. This study demonstrates that reduced RSV replication was associated with significant modulation of inflammatory and clinical markers of acute disease severity and significant improvement of the long-term pulmonary abnormalities. Studies to determine whether strategies aimed at preventing or reducing RSV replication could decrease the long-term morbidity associated with RSV infection in children should be considered.
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U2 - 10.1128/AAC.48.5.1811-1822.2004
DO - 10.1128/AAC.48.5.1811-1822.2004
M3 - Article
C2 - 15105140
AN - SCOPUS:11144355524
SN - 0066-4804
VL - 48
SP - 1811
EP - 1822
JO - Antimicrobial agents and chemotherapy
JF - Antimicrobial agents and chemotherapy
IS - 5
ER -