Interferon gamma (IFN-gamma) may reverse oral submucous fibrosis

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.