Anti-respiratory syncytial virus (RSV) neutralizing antibody decreases lung inflammation, airway obstruction, and airway hyperresponsiveness in a murine RSV model.
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 1alpha, 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.
Mejías
Asunción
A
Department of Pediatrics, Division of Pediatric Infectious Diseases, University of Texas Southwestern Medical Center at Dallas and Children's Medical Center of Dallas, Dallas, Texas 75390-9063, USA.
Chávez-Bueno
Susana
S
Ríos
Ana María
AM
Saavedra-Lozano
Jesús
J
Fonseca Aten
Mónica
M
Hatfield
Jeanine
J
Kapur
Payal
P
Gómez
Ana María
AM
Jafri
Hasan S
HS
Ramilo
Octavio
O
D000402:Airway Obstruction / Q000209:etiology / Q000628:therapy*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000914:Antibodies, Viral / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use*; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000628:therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002460:Cell Line; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D000069455:Palivizumab; D010993:Plethysmography, Whole Body; D011014:Pneumonia / Q000188:drug therapy* / Q000473:pathology*; D012129:Respiratory Function Tests; D018357:Respiratory Syncytial Virus Infections / Q000150:complications / Q000473:pathology / Q000628:therapy*; D016707:Tissue Fixation
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000914:Antibodies, Viral; D000998:Antiviral Agents; D018925:Chemokines; D016207:Cytokines; D000069455:Palivizumab