Wakelkamp I M, Gerding M N, Van Der Meer J W, Prummel M F, Wiersinga W M
Department of Endocrinology and Metabolism, Academic Medical Centre, Amsterdam, The Netherlands.
Clin Exp Immunol. 2000 Sep;121(3):453-7. doi: 10.1046/j.1365-2249.2000.01335.x.
Increased serum cytokine levels have been reported in patients with autoimmune thyroid disease, but less is known about their levels in patients with Graves' ophthalmopathy (GO). It is not known whether GO is a cell-mediated or humoral autoimmune disease. We investigated whether serum cytokines are elevated in GO patients and whether the cytokines were Th1- or Th2-derived. In addition, elevated cytokines might reflect the activity of GO, and thus we investigated whether cytokine levels could predict the clinical response to orbital radiotherapy. We studied 62 consecutive patients with moderately severe untreated GO and 62 healthy controls, matched for sex, age and smoking habits. Serum concentrations of IL-1RA, sIL-2R, IL-6, sIL-6R, tumour necrosis factor-alpha (TNF-alpha) RI and II and sCD30 were measured using highly sensitive ELISAs, in the patients before and 3 and 6 months after radiotherapy. All patients were euthyroid, with anti-thyroid drugs, before and during the entire study period. All baseline cytokine and cytokine receptor levels were significantly elevated in GO patients compared with healthy controls, except for IL-1RA. The levels did not correlate with parameters of the thyroid disease, nor with the duration, activity or severity of GO. However, backward logistic regression analysis showed that IL-6, sCD30 and TNFalphaRI were able to predict a beneficial response to orbital radiotherapy. We therefore conclude that both Th1- and Th2-derived cytokines are elevated in GO patients compared with its controls. IL-6, sCD30 and TNFalphaRI had some value for predicting therapeutic outcome to orbital irradiation, and may thus reflect active eye disease.
已有报道称自身免疫性甲状腺疾病患者血清细胞因子水平升高,但对于格雷夫斯眼病(GO)患者的细胞因子水平了解较少。目前尚不清楚GO是细胞介导的自身免疫性疾病还是体液自身免疫性疾病。我们研究了GO患者血清细胞因子是否升高,以及这些细胞因子是Th1型还是Th2型来源。此外,细胞因子升高可能反映GO的活动情况,因此我们研究了细胞因子水平是否可预测眼眶放射治疗的临床反应。我们研究了62例未经治疗的中度严重GO连续患者和62名健康对照者,两组在性别、年龄和吸烟习惯方面相匹配。在放疗前以及放疗后3个月和6个月,使用高度敏感的酶联免疫吸附测定法(ELISA)测量患者血清中白细胞介素-1受体拮抗剂(IL-1RA)、可溶性白细胞介素-2受体(sIL-2R)、白细胞介素-6(IL-6)、可溶性白细胞介素-6受体(sIL-6R)、肿瘤坏死因子-α(TNF-α)I型和II型受体以及可溶性CD30的浓度。在整个研究期间,所有患者在放疗前和放疗期间均使用抗甲状腺药物,甲状腺功能正常。与健康对照者相比,除IL-1RA外,GO患者所有基线细胞因子和细胞因子受体水平均显著升高。这些水平与甲状腺疾病参数无关,也与GO的病程、活动度或严重程度无关。然而,向后逻辑回归分析表明,IL-6、sCD30和TNF-α I型受体能够预测眼眶放射治疗的有益反应。因此,我们得出结论,与对照组相比,GO患者中Th1型和Th2型来源的细胞因子均升高。IL-6、sCD30和TNF-α I型受体在预测眼眶照射治疗结果方面具有一定价值,因此可能反映眼部疾病的活动情况。