Persistent airway inflammation after resolution of respiratory syncytial virus infection in rats.
Neurogenic inflammation is markedly potentiated in airways that are infected with respiratory syncytial virus (RSV). Aims of this study were to determine whether this potentiation persists after the virus is cleared, investigate the mechanism of postviral potentiation, and define whether prophylaxis with a MAb against the RSV fusion protein (palivizumab) prevents this effect. Thirty days after inoculation, no evidence of active RSV infection was found in the airway epithelium by plaque assay or immunostaining and no viral nucleic sequences were detected by PCR, yet capsaicin-induced plasma extravasation in the airways that were infected 30 d earlier with RSV was still significantly larger compared with pathogen-free controls. Substance P content in lung tissues and capsaicin-induced release of this peptide from sensory nerves were significantly increased at 30 d. The administration of palivizumab 24 h before virus inoculation prevented the development of abnormal neurogenic inflammatory responses. Our data suggest that the airways remain abnormally susceptible to the proinflammatory effects of sensory nerves after RSV infection is cleared, as a result of changes in sensory innervation, and that this abnormality can be prevented by passive prophylaxis against RSV.
Piedimonte
Giovanni
G
Department of Pediatrics, University of Miami School of Medicine, 1580 NW 10th Avenue, Miami, FL 33136, USA. gpiedimo@med.miami.edu
Hegele
Richard G
RG
Auais
Alexander
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000998:Antiviral Agents / Q000627:therapeutic use; D018893:Bronchoalveolar Lavage; D006801:Humans; D007223:Infant; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000821:virology; D020078:Neurogenic Inflammation / Q000276:immunology / Q000378:metabolism*; D000069455:Palivizumab; D051381:Rats; D011916:Rats, Inbred F344; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000378:metabolism; D020545:Respiratory Mucosa / Q000294:innervation / Q000821:virology; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy / Q000503:physiopathology* / Q000517:prevention & control; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000998:Antiviral Agents; D018040:Receptors, Neurokinin-1; D000069455:Palivizumab