title: Evidence of T-helper cell 2 cytokine regulation of chronic otitis media with effusion.
abstract: Cytokine and cellular patterns of effusions may reflect stages of middle ear inflammation. The local interplay between IL-2 and -4 is likely to play a crucial role in the switching of inflammation in the chronic stage. The T-helper cell 2 (Th2) cytokines IL-4, -5 and -13 and the Th2/Th1 cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) regulate the cellular and molecular processes of chronic inflammation in the middle ear and therefore the chronic condition of otitis media with effusion (OME). Early identification of the cytokine and cellular patterns of effusions can be helpful in directing the clinical treatment of OME.We hypothesized that IL-2 and the group of Th2 cytokines regulate chronic inflammation in the middle ear and chronic OME. Effusions from children with persistent OME were analysed to determine the presence of cytokines (the Th1 cytokine IL-2, the Th2 cytokines IL-4, -5 and -13 and the Th1/Th2 cytokine GM-CSF), inflammatory cells (CD4+ T cells, eosinophils, macrophages and neutrophils) and mucin. Cytokines were evaluated by means of a quantitative "sandwich"-type ELISA, inflammatory cells by means of alkaline phosphatase-anti-alkaline phosphatase immunocytostaining and mucin by means of a modified periodic acid-Schiff method based on a slot-blot technique. The cytokine pattern in effusions varied from patient to patient. GM-CSF correlated positively and IL-4 inversely with IL-2 and the increased level of IL-4 may have had an inhibitory effect on IL-2. IL-5 and -13 correlated with IL-4. Inflammatory cells correlated with cytokines as follows: CD4+ T cells with IL-2 and -4; macrophages and neutrophils with GM-CSF; and eosinophils with IL-5. Some cytokine-cellular correlations in effusions were reflected at the clinical level. The mucin content of effusions correlated with the concentrations of IL-4 (>10 pg/ml) and -13, suggesting involvement of IL-4 and -13 in upregulation of the middle ear mucin metabolism.
authors.affiliation: Institute for Cell and Molecular Biosciences & School of Biomedical Sciences, Medical Faculty, University of Newcastle upon Tyne, Newcastle upon Tyne, UK. Marina.Smirnova@ncl.ac.uk
authors.forename: Marina G
authors.initials: MG
authors.lastname: Smirnova
authors.forename: John P
authors.initials: JP
authors.lastname: Birchall
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Pearson
mesh_terms: D015496:CD4-Positive T-Lymphocytes; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D004804:Eosinophils; D005122:Exudates and Transudates / Q000166:cytology / Q000378:metabolism*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D008264:Macrophages; D009077:Mucins / Q000378:metabolism; D009504:Neutrophils; D010034:Otitis Media with Effusion / Q000378:metabolism*
chemical_list: D007378:Interleukins; D009077:Mucins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor