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白细胞介素-1α和肿瘤坏死因子-α的产生对角膜移植存活的影响。

Influence of interleukin-1alpha and tumor necrosis factor-alpha production on corneal graft survival.

作者信息

Bosnar Damir, Dekaris Iva, Gabrić Nikica, Markotić Alemka, Lazić Ratimir, Spoljarić Ninoslav

机构信息

Lions Croatian Eye Bank, Department of Ophthalmology, Holy Ghost General Hospital, Zagreb, Croatia.

出版信息

Croat Med J. 2006 Feb;47(1):59-66.

Abstract

AIM

To determine pro-inflammatory cytokine secretion from human corneas with different pathology and to establish whether cytokine profile influences corneal graft outcome.

METHOD

Secretion of both proinflammatory cytokine interleukin (IL)-1alpha and tumor necrosis factor (TNF)-alpha was measured after cultivation of 47 corneas collected from corneal graft recipients suffering from different corneal diseases. Non-inflammatory corneal diseases were keratoconus (n=8), keratoglobus (n=2), bullous keratopathy (n=11), and Groenouw stromal dystrophy type II (n=2), whereas inflammatory included vascularized corneal scar (n=14), rejected graft (n=6), and corneal ulcer (n=4). Corneas were cultivated at 37 degrees C for 24 hours and frozen until cytokine detection was measured by immunoassay. Donor corneas unsuitable for transplantation were used as controls (n=7). Corneal graft recipients were followed at least 18 months and rejection rate was calculated for each group.

RESULTS

The median concentration of IL-1alpha secreted from corneas of recipients with non-inflammatory diseases was 2.47 pg/mm(3) (range, 0.13-9.95). In inflammatory corneal diseases, IL-1alpha concentration was significantly higher (median, 5.92 pg/mm(3); range, 0.48-12.68; P=0.005). IL-1alpha production in controls (median, 0.63 pg/mm3; range, 0.36-1.29 pg/mm(3)) was significantly lower than in inflammatory corneal diseases (P<0.001) and non-inflammatory diseases (P=0.008). Low level of TNF-alpha was detected only in 5 cases of vascularized corneal scars, 3 cases of bullous keratopathy, and 3 cases of graft rejection. Rejection rate was significantly higher in inflammatory than in non-inflammatory group (46% vs <10%, respectively, P=0.008). IL-1alpha and TNF-alpha were absent from all patient's sera, confirming its local intra-ocular production.

CONCLUSION

Increased production of IL-1alpha in corneal recipients with inflammatory diseases suggests its role in corneal graft rejection in humans.

摘要

目的

测定不同病理状态下人角膜促炎细胞因子的分泌情况,并确定细胞因子谱是否影响角膜移植结果。

方法

对47例来自患有不同角膜疾病的角膜移植受者的角膜进行培养后,检测促炎细胞因子白细胞介素(IL)-1α和肿瘤坏死因子(TNF)-α的分泌情况。非炎性角膜疾病包括圆锥角膜(n = 8)、球形角膜(n = 2)、大泡性角膜病变(n = 11)和II型格罗诺夫基质营养不良(n = 2),而炎性疾病包括血管化角膜瘢痕(n = 14)、移植排斥(n = 6)和角膜溃疡(n = 4)。将角膜在37℃培养24小时后冷冻,直至通过免疫测定法检测细胞因子。将不适用于移植的供体角膜用作对照(n = 7)。对角膜移植受者进行至少18个月的随访,并计算每组的排斥率。

结果

非炎性疾病受者角膜分泌的IL-1α的中位浓度为2.47 pg/mm³(范围为0.13 - 9.95)。在炎性角膜疾病中,IL-1α浓度显著更高(中位值为5.92 pg/mm³;范围为0.48 - 12.68;P = 0.005)。对照组中IL-1α的产生(中位值为0.63 pg/mm³;范围为0.36 - 1.29 pg/mm³)显著低于炎性角膜疾病(P < 0.001)和非炎性疾病(P = 0.008)。仅在5例血管化角膜瘢痕、3例大泡性角膜病变和3例移植排斥病例中检测到低水平的TNF-α。炎性组的排斥率显著高于非炎性组(分别为46%对<10%,P = 0.008)。所有患者血清中均未检测到IL-1α和TNF-α,证实其为眼内局部产生。

结论

炎性疾病角膜受者中IL-1α产生增加表明其在人类角膜移植排斥中起作用。

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