Stalder Mario, Bîrsan Tudor, Hausen Bernard, Borie Dominic C, Morris Randall E
Transplantation Immunology, Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Transpl Int. 2005 Oct;18(10):1158-65. doi: 10.1111/j.1432-2277.2005.00119.x.
Despite previous studies suggesting that surgery cause immune suppression, the underlying biologic mechanisms have not been studied using advanced immune function assays. Unilateral nephrectomy was performed in nonhuman primates. Blood was collected before surgery and at different time-points through 14 days after surgery. Lymphocyte proliferation (expression of proliferating cell nuclear antigen in cells in S/G(2)M-phase), production of intracellular cytokines [interleukin (IL)-2, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha] and expression of surface-activation antigens (CD25, CD71) on T-lymphocytes were assessed in whole blood using flow cytometry. Results were compared with nonoperated control animals. The procedure caused a decrease of 25% in absolute lymphocyte count on postoperative day 3. Inhibition of lymphocyte proliferation was maximal on postoperative day 1 (55% normalized to preoperative values) and was detectable until postoperative day 7, when it was 25%. Expression of T-cell activation antigens was decreased during the first postoperative week with a maximum on postoperative day 1 for CD71 (29%) and on postoperative day 3 for CD25 (49%). Intracellular production of cytokines by T cells was decreased only on postoperative day 1 (50% for IL-2, 29% for IFN-gamma and 22% for TNF-alpha). Immune functions returned to presurgery values by day 14. A major surgical procedure severely inhibits lymphocyte proliferation and various T-cell functions up to 1 week postoperatively.
尽管先前的研究表明手术会导致免疫抑制，但尚未使用先进的免疫功能检测方法来研究其潜在的生物学机制。在非人类灵长类动物身上进行了单侧肾切除术。在手术前以及术后14天内的不同时间点采集血液。使用流式细胞术评估全血中淋巴细胞增殖（处于S/G(2)M期的细胞中增殖细胞核抗原的表达）、细胞内细胞因子[白细胞介素（IL）-2、干扰素（IFN）-γ、肿瘤坏死因子（TNF）-α]的产生以及T淋巴细胞表面激活抗原（CD25、CD71）的表达。将结果与未进行手术的对照动物进行比较。该手术导致术后第3天绝对淋巴细胞计数下降25%。淋巴细胞增殖的抑制在术后第1天最大（相对于术前值为55%），并且在术后第7天仍可检测到，此时为25%。T细胞激活抗原的表达在术后第一周内下降，CD71在术后第1天下降最多（29%），CD25在术后第3天下降最多（49%）。T细胞细胞内细胞因子的产生仅在术后第1天下降（IL-2下降50%，IFN-γ下降29%，TNF-α下降22%）。免疫功能在第14天恢复到术前值。一项大型外科手术在术后长达1周的时间内会严重抑制淋巴细胞增殖和各种T细胞功能。
