TNF-alpha releasing capacity of the whole blood drops after open total splenectomy, but increases after partial/subtotal or minimally invasive splenectomy

The mechanisms that induce immunodeficiency after splenectomy remain unknown. The aim of this study was to measure the cytokine releasing capacity of the whole blood as an expression of the innate immunity after total (TS) and subtotal/partial splenectomy (S/PS) in order to assess the impact of splenectomy on the individual cytokine reactivity. We prospectively collected blood before (D0) and at multiple time points after splenectomy (7 days - D7, 30 days - D30, 90 days - D90, 180 days - D180, and 360 days - D360) and measured the cytokines releasing capacity of IL-6, TNF-alpha and IL-10 from whole blood under LPS stimulation which we normalized to the monocytes number. When analyzing all splenectomies at D0, D7 and D30, normalized ΔTNF-alpha significantly dropped after splenectomy (<i>p</i> = .0038) and normalized ΔIL-6 and ΔIL-10 did not significantly change. More specifically, normalized ΔTNF-alpha dropped after TS (<i>p</i> = .0568) and significantly increased after S/PS (<i>p</i> = .0388). Open surgery induced a decrease in normalized ΔTNF-alpha (<i>p</i> = .0970), whereas minimally invasive (MI) surgery significantly increased the normalized ΔTNF-alpha releasing capacity (<i>p</i> = .0178). The cytokine levels were heterogenous between pathologies at D0, and ΔIL-6 dropped mainly in cirrhotic patients after splenectomy (all underwent TS), ΔTNF-alpha dropped in immune thrombocytopenic purpura patients (all underwent TS), but increased in spherocytosis (91% underwent S/PS) after splenectomy. Splenectomy induces a decrease of the pro-inflammatory cytokine TNF-alpha and if splenic parenchyma is spared and the surgery is performed MI, this change is hindered.

脾切除术后诱导免疫缺陷的具体机制目前仍未阐明。本研究旨在通过检测全脾切除术（total splenectomy, TS）与次全/部分脾切除术（subtotal/partial splenectomy, S/PS）后全血的细胞因子释放能力，以此反映机体固有免疫状态，进而评估脾切除术对个体细胞因子反应性的影响。
我们前瞻性采集了脾切除术术前（D0）及术后多个时间点（7天即D7、30天即D30、90天即D90、180天即D180及360天即D360）的全血样本，检测脂多糖（lipopolysaccharide, LPS）刺激下全血中IL-6、TNF-α及IL-10的释放能力，并以单核细胞计数对检测结果进行标准化处理。
对D0、D7及D30时点的全部脾切除术病例进行分析后发现，标准化后的TNF-α差值（ΔTNF-α）在脾切除术后显著下降（p = 0.0038），而标准化后的IL-6差值（ΔIL-6）与IL-10差值（ΔIL-10）无显著变化。进一步细分亚组分析显示，全脾切除术后标准化ΔTNF-α水平有所降低（p = 0.0568），次全/部分脾切除术后该指标则显著升高（p = 0.0388）。开放式手术会导致标准化ΔTNF-α水平下降（p = 0.0970），而微创（minimally invasive, MI）手术可显著提升标准化ΔTNF-α的释放能力（p = 0.0178）。
术前D0时点的细胞因子水平在不同基础疾病间存在异质性；脾切除术后，ΔIL-6水平主要在肝硬化患者（均接受全脾切除术）中出现下降，ΔTNF-α水平在免疫性血小板减少性紫癜患者（均接受全脾切除术）中降低，但在球形红细胞增多症患者（91%接受次全/部分脾切除术）中升高。
综上，脾切除术会降低促炎细胞因子TNF-α的释放水平；若术中保留脾实质且采用微创手术方式，则该变化会受到抑制。