The role of vascular endothelial growth factor in pediatric otitis media with effusion

Vascular endothelial growth factor (VEGF) is a potent and critical inducer of angiogenesis and vascular permeability, and has been shown to play an important role in inflammatory events, together with hypoxia and inflammatory cytokines. VEGF messenger ribonucleic acid (mRNA) is expressed in the middle ear in an experimental animal model of otitis media with effusion (OME) and in patients with OME. However, the protein levels of VEGF in middle ear effusions (MEEs) are unknown and the role of VEGF in the pathogenesis of OME is unclear. The goals of this study were to determine the VEGF levels in MEEs and to investigate the role of VEGF in production of MEEs by comparing these levels with those of interleukin-8 (IL-8), endotoxin, and albumin.

Forty-six MEEs obtained from 33 children (24 boys, 9 girls) were used in the study. The mean age of the subjects was 6.3 years old (range, 1-12 years old). The patients underwent myringotomy and/or insertion of a ventilation tube for treatment of OME. After myringotomy, MEEs were collected with a Juhn Tym-Tap. The samples were divided into serous and mucoid types based on observation by the naked eye. After measuring the weight of the MEE, the sample was diluted with phosphate-buffered saline and frozen until use. The concentrations of VEGF and IL-8 in the MEEs were determined by enzyme-linked immunosorbent assays, endotoxin concentrations were measured by the Limulus Amebocyte Lysate test, and albumin levels were determined using an immunoturbidimetric assay.

VEGF, endotoxin, IL-8, and albumin were detected in 100%, 89%, 98%, and 100% of the 46 MEEs, respectively. The concentrations of VEGF, endotoxin, and IL-8 were significantly higher in mucoid MEEs than in serous MEEs (p<0.01), whereas there was no significant difference in the albumin concentration between mucoid and serous MEEs. The VEGF levels were positively correlated with those of endotoxin (R(2)=0.17, p<0.05) and albumin (R(2)=0.65, p<0.01) in mucoid MEEs, but not in serous MEEs.

Our results suggest that VEGF is produced in response to bacterial components such as endotoxin in the middle ear cavity and is associated with production of mucoid MEEs by increasing serum exudation and mucosal secretion.