transforming-growth-factor-beta and Otitis-Media-with-Effusion

The study objective was to assess the levels of VEGF-A and TGF-β cytokines in the children with adenoid hypertrophy concomitant with exudative otitis media (OME) and in children with adenoid hypertrophy (HA) alone.. The study material consisted of hypertrophic adenoids removed during adenoidectomy from 39 children (20 girls and 19 boys), aged 2-7 years suffering from OME. The reference group included 41 children (19 girls and 22 boys), aged from 3 to 9 years with adenoid hypertrophy. The levels of VEGF-A and TGF-β were determined in supernatants obtained from phytohemagglutinin-stimulated cell cultures of the adenoids using a commercial enzyme-linked immunosorbent assay kit.. 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, P < 0.001, respectively). ROC analysis revealed that the area under the curve (AUC) for VEGF-A was 0.952 with diagnostic sensitivity and specificity of 95%, whereas for TGF-β it was 0.902 with 60% sensitivity and the same specificity as for VEGF-A. There was no significant difference between the AUC for VEGF-A and TGF-β (P = 0.573).. The changes in the levels of VEGF-A and TGF-β may indicate bacterial pathogen as one of the causes of exudative otitis media in children. Determination of VEGF-A and TGF-β could be used as additional and objective tests to confirm the clinical diagnosis.

Topics: Adenoidectomy; Adenoids; Area Under Curve; Child; Child, Preschool; Exudates and Transudates; Female; Humans; Hypertrophy; Male; Otitis Media; Otitis Media with Effusion; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A

Nontypeable Haemophilus influenzae (NTHi) is associated with chronic otitis media (COM). In this study, we generated a murine model of COM by using eustachian tube (ET) obstruction and NTHi (10(7) CFU) inoculation into the tympanic bulla, and we investigated the relationship between regulatory T cells (Treg) and chronic inflammation in the middle ear. Middle ear effusions (MEEs) and middle ear mucosae (MEM) were collected at days 3 and 14 and at 1 and 2 months after inoculation. Untreated mice served as controls. MEEs were used for bacterial counts and to measure the concentrations of cytokines. MEM were collected for histological evaluation and flow cytometric analysis. Inflammation of the MEM was prolonged throughout this study, and the incidence of NTHi culture-positive MEE was 38% at 2 months after inoculation. The levels of interleukin-1β (IL-β), tumor necrosis factor alpha, IL-10, and transforming growth factor β were increased in the middle ear for up to 2 months after inoculation. CD4(+) CD25(+) FoxP3(+) Treg accumulated in the middle ear, and the percentage of Treg in the MEM increased for up to 2 months after inoculation. Treg depletion induced a 99.9% reduction of bacterial counts in MEEs and also significantly reduced the ratio of NTHi culture-positive MEE. The levels of these cytokines were also reduced in MEEs. In summary, we developed a murine model of COM, and our findings indicate that Treg confer infectious tolerance to NTHi in the middle ear.

Topics: Animals; Chronic Disease; Disease Models, Animal; Ear, Middle; Eustachian Tube; Haemophilus Infections; Haemophilus influenzae; Inflammation; Interleukin-10; Interleukin-1beta; Lymphocyte Count; Mice; Mice, Inbred BALB C; Mucous Membrane; Otitis Media with Effusion; T-Lymphocytes, Regulatory; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

To characterize the existence and role of transforming growth factor-beta (TGF-beta) in otitis media with effusion (OME).. Retrospective.. The levels of two major TGF-beta isoforms, TGF-beta1 and TGF-beta2, in the middle ear effusions (MEEs) of 44 children were evaluated using enzyme-linked immunospecific assays (ELISAs). Forty-eight MEEs were separated into three clinically relevant groups (i.e., serous, mucoid, and purulent), and TGF-beta levels were correlated with clinical parameters of disease for these MEEs.. Both TGF-beta1 and TGF-beta2 were present in the samples. Mean levels of TGF-beta1 (920.36 +/- 437.75 pg/mg total protein) were generally 100-fold greater than those of TGF-beta2 (9.65 +/- 11.19 pg/mg total protein). TGF-beta1 levels were elevated in association with a history of previous tympanostomy tube placements (TTPs) (P = .029) and mucoid effusions (P = .042). TGF-beta2 levels were elevated in association with a history of previous TTPs (P = .100) and chronic (i.e., serous or mucoid) effusions (P = .003).. TGF-beta1 is present in the MEEs of children with OME. Furthermore, TGF-beta1 and TGF-beta2 levels were elevated differentially in the presence of chronic disease indicators in OME, suggesting that these isoforms may have differing roles in the inflammatory processes that characterize OME.

Topics: Child; Child, Preschool; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Exudates and Transudates; Female; Humans; Infant; Isomerism; Male; Middle Ear Ventilation; Otitis Media with Effusion; Otitis Media, Suppurative; Recurrence; Risk Factors; Transforming Growth Factor alpha; Transforming Growth Factor beta