INHIBITORY EFFECT OF PENTOXIFYLLINE ON HLA-DR EXPRESSION AND GLYCOSAMINOGLYCAN SYNTHESIS BY RETROBULBAR FIBROBLASTS

Objective. Glycosaminoglycan (GAG) production by retroocular fibroblas ts (REF) is increased in patients with thyroid-associated ophthalmopat hy (TAO). Various cytokines stimulate REFs to proliferate and elaborat e GAG, free oxygen radicals as well as induce HLA-DR expression on the se cells. Pentoxifyllin (Ptx) regulates the production of several cyto kines 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 GA G synthesis by REF and IFN-gamma induced HLA-DR expression. Design. RE F derived from extraocular muscles of healthy subjects were cultured w ithout and with cytokines (IFN-gamma, TNF alpha and IL-1) and the effe ct of Ptx on the production of GAG by REF and HLA-DR expression was de termined. Measurements. Glycosaminoglycan was measured by incorporatio n of (H-3) glycosamine into GAG. HLA-DR expression was analyzed by flu orescence activated cell sorter. Results. Both spontaneous and cytokin e 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 funct ion of lymphocytes infiltrating the retro-orbital tissues, and which a re instrumental in TAO.