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DOI: 10.1055/s-2007-978919
© Georg Thieme Verlag Stuttgart · New York
Inhibitory Effect of Pentoxifylline on HLA-DR Expression and Glycosaminoglycan Synthesis by Retrobulbar Fibroblasts
Publication History
1997
1998
Publication Date:
20 April 2007 (online)
![](https://www.thieme-connect.de/media/hmr/199808/lookinside/thumbnails/10.1055-s-2007-978919-1.jpg)
Objective. Glycosaminoglycan (GAG) production by retro-ocular fibroblasts (REF) is increased in patients with thyroid-associated ophthalmopathy (TAO). Various cytokines stimulate REFs to proliferate and elaborate GAG, free oxygen radicals as well as induce HLA-DR expression on these cells. Pentoxifyllin (Ptx) regulates the production of several cytokines including tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1) and, interferon gamma (IFN-gamma). We wished in this study to determine whether Ptx modified the spontaneous and cytokine-induced GAG synthesis by REF and IFN-gamma induced HLA-DR expression. Design. REF derived from extraocular muscles of healthy subjects were cultured without and with cytokines (IFN-gamma, TNF alpha and IL-1) and the effect of Ptx on the production of GAG by REF and HLA-DR expression was determined. Measurements. Glycosaminoglycan was measured by incorporation of (3H) glycosamine into GAG. HLA-DR expression was analyzed by fluorescence activated cell sorter. Results. Both spontaneous and cytokine induced GAG synthesis by REF was inhibited by Ptx (100, 500 and 1000 mg/l, respectively). IFN-gamma (50, 100 and 500 U/ml) induced a dose-dependent increase in the expression of HLA-DR molecules by REF. Ptx, which was not toxic to REF, inhibited HLA-DR expression on those cells dose-dependently. Conclusions. Our in vitro results suggest that Ptx reduces cytokine-induced GAG production and HLA-DR expression by REF. It thus has potential as a therapeutic agent which regulates the function of lymphocytes infiltrating the retro-orbital tissues, and which are instrumental in TAO.
Key words
Pentoxifylline - Cytokines - Retro-orbital fibroblasts - Thyroid associated-ophthalmopathy - Glucosaminoglycans