title: Interferon gamma (IFN-gamma) may reverse oral submucous fibrosis.
abstract: Oral submucous fibrosis (OSF) is a chronic disease of the oral cavity and oropharyngx characterised by fibrosis in the submucosa leading to progressive limitation of the mouth opening. Interferon gamma (IFN-gamma) is a known anti-fibrotic cytokine. In this study we have investigated: a) the effect of IFN-gamma on collagen synthesis by arecoline-stimulated OSF fibroblasts in vitro (n=5), b) the effect of intra-lesional IFN-gamma on the fibrosis of OSF patients (n=29) and c) the immunohistochemical analysis of pre- and post-treatment inflammatory cell infiltrates and cytokine levels in the lesional tissue (n=29). The results show that the increased collagen synthesis in vitro in response to arecoline was inhibited in the presence of IFN-gamma (0.01-10.0 U/ ml) in a dose-related way. In an open uncontrolled study intra-lesional IFN-gamma treatment showed improvement in the patients mouth opening from an inter-incisal distance before treatment of 21 +/- 7 mm, to 30 +/- 7 mm immediately after treatment and 30 +/- 8 mm 6-months later, giving a net gain of 8 +/- 4 mm (42%) (range 4-15 mm). Patients also reported reduced burning dysaesthesia and increased suppleness of the buccal mucosa. The post-treatment immunohistochemistry showed a decreased amount of inflammatory cell infiltrate and an altered level of cytokines compared with the pre-treatment lesional tissue. The effect of IFN-gamma on collagen synthesis appears to be a key to the treatment of these patients, and intra-lesional injections of the cytokine may have a significant therapeutic effect on OSF.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University College London, UK.
authors.forename: M F
authors.initials: MF
authors.lastname: Haque
authors.forename: S
authors.initials: S
authors.lastname: Meghji
authors.forename: R
authors.initials: R
authors.lastname: Nazir
authors.forename: M
authors.initials: M
authors.lastname: Harris
mesh_terms: D001114:Areca / Q000009:adverse effects*; D001115:Arecoline / Q000494:pharmacology; D002478:Cells, Cultured; D018679:Cholinergic Agonists / Q000494:pharmacology; D003094:Collagen / Q000096:biosynthesis; D016207:Cytokines / Q000032:analysis; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D015552:Injections, Intralesional; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009061:Mouth Mucosa / Q000473:pathology; D009914:Oral Submucous Fibrosis / Q000188:drug therapy* / Q000209:etiology*; D010946:Plants, Medicinal; D010947:Plants, Toxic; D011994:Recombinant Proteins; D016176:T-Lymphocyte Subsets; D014030:Tobacco, Smokeless
chemical_list: D018679:Cholinergic Agonists; D016207:Cytokines; D011994:Recombinant Proteins; D001115:Arecoline; D007371:Interferon-gamma; D003094:Collagen