[Immunomodulatory effect of pentoxifylline in Graves ophthalmopathy]

In the pathomechanism of the thyroid associated ophthalmopathy (TAO) the inflammatory cytokines produced by infiltrating lymphocytes of the retroorbital tissues are involved. The activated lymphocytes have been shown to secrete a number of cytokines including tumour necrosis factor-alpha, interleukin-1 and interferon-gamma. The widely used immunosuppressive therapies have potential serious side effects. The pentoxifylline (Ptx) is known to have effect on production of cytokines. The aim of this study was to investigate the effect of Ptx on expression of HLA-DR molecules and production of glycosaminoglycan of human retroorbital tissue cultures and potential efficacy in patients with TAO. It was found that pentoxifylline (Ptx) was able to inhibit significantly the HLA-DR expression and glycosaminoglycan synthesis induced by inflammatory cytokines including TNF-alpha, IFN-gamma and IL-1. Ten patients with untreated moderate severe ophthalmopathy (8 female and 2 male) were excluded from steroid treatment due diabetes mellitus and psychiatric disease. Classification of eye changes was made by NOSPECS categories and total eye score. All patients were euthyroid during the study and was no remarkable difference in thyroid function and eye symptoms. Before and during Ptx therapy the laboratory parameters were also determined including glycosaminoglycan. TNF-alpha, anti-TSH-receptor, anti-eye muscle, anti-thyroglobulin and anti-thyroid peroxidase antibodies in the patients'sera. It was found a remarkable improvement in the eye symptoms in eight of ten patients. The levels of glycosaminoglycan (uronic acid) and TNF-alpha gradually decreased in eight patients who considered to be responders. The levels of uronic acid in plasma of the responders were found to be significantly lower after Ptx treatment. Before Ptx therapy the TNF-alpha in the sera was not different remarkably in non-responders and responders. After 4 weeks Ptx treatment the TNF-alpha decreased significantly in responders compared to non-responders (20.9 +/- 4.8 pg/ml v. s. 28.3 +/- 6.1 pg/ml) (p < 0.01). The titre of anti-eye muscle antibodies were found to be lower at the end of observation, however, the anti-thyroid antibodies were not changed remarkably. It was concluded that Ptx in the majority of patients (8/10) has a beneficial effect on inflammatory symptoms of TAO and laboratory parameters and suggested to use as an additive therapy, however, further comparative studies are required for final evaluation of Ptx in the treatment of TAO.