Vascular endothelial growth factor and transforming growth factor β in hypertrophic adenoids in children suffering from otitis media with effusion
Introduction
Adenotonsillar hypertrophy (ATH) is considered to be the most common otolaryngological disorder in children. However, the causes of ATH are not fully understood. It is believed that genetic, hormonal and immune factors play a substantial role in the pathogenesis of the disorder [1]. Recurrent or chronic tonsillitis contributes to chronic cellular activation and humoral immune response, and also to the development of otitis media with effusion (OME) in children [2], [3].
Monitoring the course of exudative otitis media may be based on the measurement of individual cytokine levels during the disease course in children. A number of cytokines, including IL-1β, IL-6, IL-8, TNF-α and, to a lesser extent, IL-3, IL-5 and INF-γ are responsible for local inflammatory reactions [4]. IL-2 and IL-4 play an important role during the acute phase, while IL-5, IL-8 and transforming growth factor β (TGF-β) are produced during the chronic phase of inflammation [4], [5]. Subclinical bacterial infections, injections of bacterial and viral components and allergies all cause the release of inflammatory cytokines such as TNF-α, IL-1, IL-6, IL-8. Moreover, increased levels of vascular endothelial growth factor (VEGF) and TGF-β levels are observed [6], [7].
VEGF is produced by the middle ear mucosa and its concentration increases in the exudate and middle ear mucosa in patients with otitis media [7], [8], [9]. Bacterial infections increase the levels of both VEGF and its receptors. Elevated cytokine concentrations lead to increased vascular permeability and elevated secretion of exudative fluid. Moreover, they affect the infection of inflammatory cells of the mucous membrane, thus leading to neovascularization within the middle ear [8], [9]. In turn, TGF-β, as an anti-inflammatory cytokine, influences the inhibition of immune reactions. Its levels are elevated in serum exudates of patients with OME [10]. However, significant proportions of TGF-β1 are found in the mucosal effusions following long-lasting inflammatory processes. TGF-β levels are high in the majority of chronic inflammatory processes, while increasing in acute inflammation in patients with Streptococcus pneumoniae or Haemophilus influenzae. TGF-β promotes the development of scarring at the perforation border, which is the cause of slow healing of the eardrum in exudative ear infection [10], [11].
The study objective was to assess the levels of VEGF-A and TGF-β in PHA (phytohemagglutinin)-stimulated cell cultures of the adenoid hypertrophy in the group of children with adenoids who suffer from exudative otitis media (OME) of 3 months’ duration and in the group of children with adenoid hypertrophy (HA).
Section snippets
Patients
The study material consisted of hypertrophic adenoids removed during adenoidectomy from 39 children (20 girls and 19 boys), aged 2–7 years (mean age 4.40 ± 1.40), suffering from adenoid hypertrophy coexisting with otitis media with effusion (OME) lasting for three months or longer. The reference group consisted of 41 children (19 girls and 22 boys), aged from 3 to 9 years (mean age 5.08 ± 1.27 years) with adenoid hypertrophy (HA), but without otitis media. All the children were clinically free
Results
VEGF-A in the reference group and TGF-β in the study group were normally distributed (W = 0.950, P = 0.365 and W = 0.949, P = 0.351, respectively), whereas TGF-β in the reference and VEGF-A in the study group were non-normally distributed (W = 0.893, P = 0.031 and W = 0.873, P = 0.013, respectively). The median VEGF-A and mean TGF-β concentrations in the study group were significantly higher than those in the reference group (503 pg/mL versus 201 pg/mL, P < 0.001 and 224 pg/mL versus 132 pg/mL,
Discussion
Adenoids, also known as pharyngeal tonsils, develop early in fetal life. However, they continue to grow until approximately the age of 7 as a result of being in constant contact with antigens [12]. Due to their location, they constitute the first line of defense when the body is invaded. They are where humoral and cellular reactions occur in response to antigens released during inhalation, from food and intrinsic antigens [13]. Adenoids are covered with pseudostratified ciliated epithelium with
Conclusion
The results obtained in our study suggest that VEGF-A and TGF-β may affect the immune function of hypertrophic adenoids. High levels of VEGF-A and TGF-β may indicate a bacterial pathogen as one of the causes of exudative otitis media in children. Determination of VEGF-A and TGF-β could be used as an additional and objective test to confirm the clinical diagnosis.
Contributorship
B Z-R and BC researched literature and conceived the study. BS was involved in patients recruitment. B Z-R was involved in gaining ethical approval and wrote the first draft of the manuscript. BC was involved in protocol development and data analysis. All authors reviewed and edited the manuscript and approved of the final version of the manuscript.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Ethical approval
This clinical investigation (R-I-002/205/2017) was approved by the Bioethical Committee of Medical University of Bialystok, Poland.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
References (22)
- et al.
Association of Ugrp2 gene polymorphisms with adenoid hypertrophy in the pediatric population
Braz. J. Otorhinolaryngol.
(2018) - et al.
The role of vascular endothelial growth factor in pediatric otitis media with effusion, Auris Nasus
Larynx. 38
(2011) - et al.
Upper airway cough syndrome in children and two inflammatory factors: TRPV1 and TGF-β2
Int. J. Pediatr. Otorhinolaryngol. 78
(2014) - et al.
Cytokines and chemokines
J. Allergy Clin. Immunol
(2003,) - et al.
IL-6 promotes the expression of vascular endothelial growth factor through the p38 signalling pathway in hypertrophied adenoids in children
Int. J. Pediatric Otorhinolaryngol.
(2013) - et al.
The Diagnosis and Management of Acute Otitis Media
Pediatrics
(2013) - et al.
Immunoregulatory cytokines and chronic tonsillitis, Bosn
J. Basic. Med. Sc.
(2013) - et al.
Role of the pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6 and interleukin-8 in the pathogenesis of the otitis media with effusion
Eur. Cytokine Netw.
(2002) - et al.
Pro-inflammatory interleukins in middle ear effusions from atopic and non-atopic children with chronic otitis media with effusion
Eur. Arch. Otorhinolaryngol.
(2016) - et al.
The role of vascular endothelial growth factors and fibroblast growth factors in angiogenesis during otitis media
Audiol. Neurootol. 17
(2012)
Expression of vascular endothelial growth factor in otitis media
Acta Otolaryngol.
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