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Published ahead of print on May 5, 2005, doi:10.1164/rccm.200412-1693OC
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American Journal of Respiratory and Critical Care Medicine Vol 172. pp. 233-237, (2005)
© 2005 American Thoracic Society
doi: 10.1164/rccm.200412-1693OC

Original Article

Neurotrophin Overexpression in Lower Airways of Infants with Respiratory Syncytial Virus Infection

Luca Tortorolo, Arianna Langer, Giancarlo Polidori, Giovanni Vento, Barbara Stampachiacchere, Luigi Aloe and Giovanni Piedimonte

Department of Pediatrics, Catholic University School of Medicine; Institute of Neurobiology, Italian National Research Council, Rome, Italy; and Batchelor Children's Research Institute, and Departments of Pediatrics, Medicine, and Molecular/Cellular Pharmacology, University of Miami School of Medicine, Miami, Florida

Correspondence and requests for reprints should be addressed to Giovanni Piedimonte, M.D., Pediatric Pulmonary Research, Batchelor Children's Research Institute, 1580 NW 10th Avenue (D-820), Miami, FL 33136. E-mail: gpiedimo{at}med.miami.edu

Rationale: Nerve growth factor and its receptors are upregulated in the lungs of weanling rats with lower respiratory tract infection caused by the respiratory syncytial virus (RSV), and this is a major mechanism of the inflammatory response against the virus. However, no information is available in humans. Objectives: We sought to determine whether the expression of neurotrophic factors and receptors is increased in human infants infected with RSV. Methods: We used a highly sensitive immunoassay to measure the concentrations of nerve growth factor and brain-derived neurotrophic factor proteins in serum samples and in the supernatants and cell fractions of nonbronchoscopic bronchoalveolar lavage fluid. We also used immunofluorescence to detect expression in airway cells of the tyrosine kinase receptor TrkA, which binds nerve growth factor with high affinity. Samples were obtained at 24 and 48 hours postintubation from 31 mechanically ventilated infants: 15 patients with RSV infection, 5 patients with respiratory infection negative for RSV, and 11 postsurgical patients without respiratory infection. Main Results: Data show significantly higher concentrations of both neurotrophins in the cell fractions of bronchoalveolar lavage samples obtained from infants with RSV infection compared with control infants, whereas no significant difference was found in supernatants or serum samples. We also detected tyrosine kinase receptor immunoreactivity only in cells from airways infected with RSV. Conclusions: We conclude that neurotrophic factors and receptors are overexpressed in human airways infected by RSV, and may contribute to airway inflammation and hyperreactivity.

Key Words: asthma • brain-derived neurotrophic factor • bronchiolitis • nerve growth factor • pneumonia




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