Neurotrophin overexpression in lower airways of infants with respiratory syncytial virus infection.
BACKGROUND
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.


OBJECTIVE
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.


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.
Tortorolo
Luca
L
Pediatric Pulmonary Research, Batchelor Children's Research Institute, 1580 NW 10th Avenue (D-820), Miami, FL 33136, USA.
Langer
Arianna
A
Polidori
Giancarlo
G
Vento
Giovanni
G
Stampachiacchere
Barbara
B
Aloe
Luigi
L
Piedimonte
Giovanni
G
D019208:Brain-Derived Neurotrophic Factor / Q000097:blood / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016022:Case-Control Studies; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008168:Lung / Q000378:metabolism*; D008297:Male; D009414:Nerve Growth Factors / Q000097:blood / Q000378:metabolism*; D011446:Prospective Studies; D020917:Receptor, trkA / Q000378:metabolism; D012121:Respiration, Artificial; D018357:Respiratory Syncytial Virus Infections / Q000097:blood / Q000378:metabolism* / Q000628:therapy
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020917:Receptor, trkA