Chung Wen Yuan, Pollard Cristina A, Kumar Rohan, Drogemuller Christopher J, Naziruddin Bashoo, Stover Cordula, Issa Eyad, Isherwood John, Cooke Jill, Levy Marlon F, Coates P Toby H, Garcea Giuseppe, Dennison Ashley R
Department of Hepatobiliary and Pancreatic Surgery, Leicester General Hospital, Leicester, UK.
Australian Islet Consortium, Royal Adelaide Hospital, South Australia, Australia.
Ann Transl Med. 2021 Jan;9(2):98. doi: 10.21037/atm-20-3519.
The initial response to islet transplantation and the subsequent acute inflammation is responsible for significant attrition of islets following both autologous and allogenic procedures. This multicentre study compares this inflammatory response using cytokine profiles and complement activation.
Inflammatory cytokine and complement pathway activity were examined in two cohorts of patients undergoing total pancreatectomy followed either by autologous (n=11) or allogenic (n=6) islet transplantation. Two patients who underwent total pancreatectomy alone (n=2) served as controls.
The peak of cytokine production occurred immediately following induction of anaesthesia and during surgery. There was found to be a greater elevation of the following cytokines: TNF-alpha (P<0.01), MCP-1 (P=0.0013), MIP-1α (P=0.001), MIP-1β (P=0.00020), IP-10 (P=0.001), IL-8 (P=0.004), IL-1α (P=0.001), IL-1ra (0.0018), IL-10 (P=0.001), GM-CSF (P=0.001), G-CSF (P=0.0198), and Eotaxin (P=0.01) in the allogenic group compared to autografts and controls. Complement activation and consumption was observed in all three pathways, and there were no significant differences in between the groups although following allogenic transplantation ∆IL-10 and ∆VEGF levels were significantly elevated those patients who became insulin-independent compared with those who were insulin-dependent.
The cytokine profiles following islet transplantation suggests a significantly greater acute inflammatory response following allogenic islet transplantation compared with auto-transplantation although a significant, non-specific inflammatory response occurs following both forms of islet transplantation.
胰岛移植后的初始反应及随后的急性炎症是自体和异体胰岛移植术后胰岛显著减少的原因。这项多中心研究使用细胞因子谱和补体激活来比较这种炎症反应。
在两组接受全胰切除术后分别进行自体（n = 11）或异体（n = 6）胰岛移植的患者中检测炎症细胞因子和补体途径活性。两名仅接受全胰切除术的患者（n = 2）作为对照。
细胞因子产生的峰值在麻醉诱导后及手术期间立即出现。发现以下细胞因子有更大程度的升高：与自体移植组和对照组相比，异体移植组中的肿瘤坏死因子-α（P < 0.01）、单核细胞趋化蛋白-1（P = 0.0013）、巨噬细胞炎性蛋白-1α（P = 0.001）、巨噬细胞炎性蛋白-1β（P = 0.00020）、干扰素诱导蛋白-10（P = 0.001）、白细胞介素-8（P = 0.004）、白细胞介素-1α（P = 0.001）、白细胞介素-1受体拮抗剂（0.0018）、白细胞介素-10（P = 0.001）、粒细胞-巨噬细胞集落刺激因子（P = 0.001）、粒细胞集落刺激因子（P = 0.0198）和嗜酸性粒细胞趋化因子（P = 0.01）。在所有三条途径中均观察到补体激活和消耗，尽管在异体移植后，与胰岛素依赖患者相比，实现胰岛素非依赖的患者中，白细胞介素-10和血管内皮生长因子水平显著升高，但各组之间没有显著差异。
胰岛移植后的细胞因子谱表明，与自体移植相比，异体胰岛移植后的急性炎症反应明显更大，尽管两种形式的胰岛移植后都会发生显著的非特异性炎症反应。
