Gürol A O, Kurşun A O, Süzergöz F, Küçüksezer U C, Kiran B, Kaya S, Küçük M, Deniz G, Yilmaz M T
Istanbul University, Institute for Experimental Medical Research, Department of Immunology, Capa, 34280 Istanbul, Turkey.
Transplant Proc. 2005 Jun;37(5):2375-8. doi: 10.1016/j.transproceed.2005.03.097.
Interleukin-1beta (IL-1beta) is one of the proinflammatory cytokines that may mediate primary nonfunction of islets of Langerhans, limiting the success of allogeneic transplantation. The aim of this study was to assess differences between the secretion of IL-1beta as well as glycemia in peri- and long-term periods of intraportal islet allo-transplantation with or without cyclosporine (CyA) immunosuppression. Inbred Wistar albino rats were transplanted intraportally with rat islets isolated by collagenase digestion. The two recipient groups (6 rats/group) were: group 1, control, islet transplantation (ITX) without any treatment and group 2, CyA-treated via the femoral muscle on days -1, 0, +1, and +2. Serum IL-1beta (pg/mL) levels were measured by ELISA on days 0 (pre-ITX), +1, +2, and +195. Tail vein blood was used to evaluate glycemia (mg/dL). No major differences were observed in IL-1beta secretion on days 0, +1, or +195 between the groups. Immunosuppressive treatment produced significantly lower secretion in group 2 (P < .002) on day +2. Significantly greater secretions were detected at days +195, +1, and +195 compared to days 0, +2, and +2, respectively (P < .002; P < .008; P < .002). Positive correlations were observed between IL-1beta levels on days +1 and +2 (r = 0.845, P < .034). The mean values in groups 1 and 2 on days 0, +1, and +2 were 140.6 +/- 4.62 vs 119.1 +/- 12.12, 73.1 +/- 19.59 vs 88.3 +/- 14.08, 106.5 +/- 13.79 vs 92.5 +/- 15.8, respectively. No animal in group 1 displayed glycemia while three group 2 animals did at day +195. However, a negative correlation was found between IL-1beta on day 0 and glycemia on day +195 (r = -0.999, P < .026). Our results suggest that IL-1beta secretion, which is detrimental for islet engraftment, decreases at peritransplant day +2, but is upregulated during long-term graft survival both in controls and in CyA-treated recipients.
白细胞介素-1β(IL-1β)是一种促炎细胞因子,可能介导朗格汉斯胰岛的原发性无功能,限制同种异体移植的成功率。本研究的目的是评估在门静脉内胰岛同种异体移植的围手术期和长期,使用或不使用环孢素(CyA)免疫抑制时,IL-1β分泌以及血糖之间的差异。近交系Wistar白化大鼠通过胶原酶消化分离的大鼠胰岛进行门静脉内移植。两个受体组(每组6只大鼠)分别为:第1组,对照组,未进行任何处理的胰岛移植(ITX);第2组,在第-1、0、+1和+2天通过股部肌肉给予CyA治疗。在第0天(ITX前)、+1、+2和+195天通过ELISA测量血清IL-1β(pg/mL)水平。用尾静脉血评估血糖(mg/dL)。两组在第0、+1或+195天的IL-1β分泌未观察到主要差异。免疫抑制治疗使第2组在第+2天的分泌显著降低(P < 0.002)。与第0、+2和+2天相比,在第+195、+1和+195天分别检测到显著更高的分泌(P < 0.002;P < 0.008;P < 0.002)。在第+1和+2天的IL-1β水平之间观察到正相关(r = 0.845,P < 0.034)。第1组和第2组在第0、+1和+2天的平均值分别为140.6±4.62对119.1±12.12、73.1±19.59对88.3±14.08、106.5±13.79对92.5±15.8。第1组没有动物出现高血糖,而第2组有3只动物在第+195天出现高血糖。然而,在第0天的IL-1β与第+195天的血糖之间发现负相关(r = -0.999,P < 0.026)。我们的结果表明,对胰岛植入有害的IL-1β分泌在移植后第+2天减少,但在对照组和CyA治疗的受体中长期移植物存活期间均上调。