Inhibitory effect of pentoxifylline on HLA-DR expression and glycosaminoglycan synthesis by retrobulbar fibroblasts.
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.


METHODS
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.


METHODS
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.
III. Department of Medicine-Endocrinology, Kenezy Teaching Hospital, Debrecen, Hungary.
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Balazs
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Kiss
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Farid
D046508:Culture Techniques; D005123:Eye / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D016166:Free Radical Scavengers; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006684:HLA-DR Antigens / Q000032:analysis*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D010431:Pentoxifylline / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016166:Free Radical Scavengers; D006025:Glycosaminoglycans; D006684:HLA-DR Antigens; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D010431:Pentoxifylline