Balázs C, Kiss E, Farid N R
III. Department of Medicine-Endocrinology, Kenézy Teaching Hospital, Debrecen, Hungary.
Acta Microbiol Immunol Hung. 1997;44(2):173-9.
Glycosaminoglycan (GAG) accumulation produced by retroocular fibroblasts (REF) has been observed in patients with thyroid-associated ophthalmopathy (TAO). Various cytokines are able to express HLA-DR molecules and stimulate the REF to proliferate GAG and free oxygen radicals. Pentoxifylline (Ptx) is known to have complex immunomodulatory effects on production of cytokines including interferon gamma (IFN-gamma). Ptx has been assumed to inhibit the cytokine-induced production of GAG and HLA-DR expression. We wished to determine whether Ptx has an effect on the IFN-gamma induced HLA-DR expression and influences the spontaneous and cytokine-induced GAG synthesis of REF. REF derived from extraocular muscles of healthy subjects were cultured without and with IFN-gamma. The effect of Ptx on expression of HLA-DR molecules and the production of GAG by REF was determined. Glycosaminoglycan was measured by incorporation of (3H)glycosamine into GAG. HLA-DR expression was analysed by fluorescence activated cell sorter. IFN-gamma (50, 100 and 500 U/ml) induced an increase in expression of HLA-DR molecules of REF. Ptx was proved not to be toxic for cultured cells. This drug was able to dose-dependently inhibit HLA-DR expression of REF. Both spontaneous and IFN-gamma-induced GAG synthesis of REF was inhibited by Ptx (100, 500 and 1000 mg/l, respectively). Due to in vitro inhibitory effects, Ptx is potentially able to modify the antigen presentation and the GAG synthesis by REF and it might be a useful therapeutical drug in the treatment of TAO.
在甲状腺相关性眼病（TAO）患者中，已观察到眼后成纤维细胞（REF）产生的糖胺聚糖（GAG）积聚。多种细胞因子能够表达HLA - DR分子并刺激REF增殖GAG和产生游离氧自由基。己酮可可碱（Ptx）已知对包括干扰素γ（IFN - γ）在内的细胞因子产生具有复杂的免疫调节作用。Ptx被认为可抑制细胞因子诱导的GAG产生和HLA - DR表达。我们希望确定Ptx是否对IFN - γ诱导的HLA - DR表达有影响，并影响REF的自发和细胞因子诱导的GAG合成。将源自健康受试者眼外肌的REF在有无IFN - γ的情况下进行培养。测定Ptx对REF的HLA - DR分子表达和GAG产生的影响。通过将（3H）葡糖胺掺入GAG中来测量GAG。通过荧光激活细胞分选仪分析HLA - DR表达。IFN - γ（50、100和500 U/ml）诱导REF的HLA - DR分子表达增加。已证明Ptx对培养细胞无毒。该药物能够剂量依赖性地抑制REF的HLA - DR表达。Ptx（分别为100、500和1000 mg/l）抑制了REF的自发和IFN - γ诱导的GAG合成。由于其体外抑制作用，Ptx可能能够改变REF的抗原呈递和GAG合成，它可能是治疗TAO的一种有用的治疗药物。
