Torres Manuel B, Vega Virginia L, Bedri Mazen, Saad Daniel, Trentzsch Heiko, Reeves Roger H, De Maio Antonio
Division of Pediatric Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
J Surg Res. 2005 Nov;129(1):101-6. doi: 10.1016/j.jss.2005.06.008. Epub 2005 Aug 8.
Splenectomy is clinically indicated in certain cases of hypersplenism and splenic trauma. However, it is associated with serious complications, in particular, reduced clearance of encapsulated organisms and a high incidence of sepsis, which has been coined overwhelming post-splenectomy sepsis (OPSS). In addition to the role of the spleen in the clearance of microorganisms, this organ may be involved in regulation of the inflammatory response. We investigated the effect of splenectomy on the inflammatory process induced by LPS in a murine model that resembles, in part, the pathophysiological aspects of sepsis.
Male mice (8-weeks-old) from different inbred strains were randomized into three groups: splenectomized (SPX), sham operated (SHAM), and non-operated controls (NoOp). After 9 days of recovery, mice were injected with LPS (15 mg/kg) and cytokine plasma levels were measured by ELISA at 1.5 or 6 h after injection. Peritoneal macrophages (PMphi) were isolated from the three groups, and cytokine production was evaluated after incubation with LPS in culture conditions.
IL-10 plasma levels were elevated in SPX A/J mice (6.7 +/- 0.4 mug/ml) after injection of LPS (15 mg/kg) compared to NoOp A/J mice (4.2 +/- 0.2 mug/ml, P < 0.05). Similar elevation in IL-10 plasma levels was detected in SPX DBA/2J mice as compared to NoOp DBA/2J mice, but not in C57BL/6J and BALB/cJ mice. In contrast, SPX AKR mice displayed lower IL-10 levels than NoOp mice. PMphis from SPX A/J mice produced elevated levels of IL-10 compared to PMphis from SHAM or NoOp A/J mice, mimicking the in vivo observations.
Our data suggest that the spleen plays an important role in modulating the inflammatory process induced by LPS, extending beyond passive clearance of encapsulated organisms. In addition, the contribution of the spleen to the inflammatory process may be influenced by the genetic background.
脾切除术在某些脾功能亢进和脾外伤病例中具有临床指征。然而，它与严重并发症相关，特别是包膜菌清除减少和败血症发生率高，这被称为脾切除术后暴发性感染（OPSS）。除了脾脏在清除微生物中的作用外，该器官可能还参与炎症反应的调节。我们在一个部分类似于败血症病理生理方面的小鼠模型中研究了脾切除术对脂多糖（LPS）诱导的炎症过程的影响。
将来自不同近交系的8周龄雄性小鼠随机分为三组：脾切除组（SPX）、假手术组（SHAM）和未手术对照组（NoOp）。恢复9天后，给小鼠注射LPS（15mg/kg），并在注射后1.5或6小时通过酶联免疫吸附测定（ELISA）测量细胞因子血浆水平。从三组中分离出腹腔巨噬细胞（PMphi），并在培养条件下与LPS孵育后评估细胞因子产生情况。
与未手术的A/J小鼠（4.2±0.2μg/ml，P<0.05）相比，注射LPS（15mg/kg）后，脾切除的A/J小鼠血浆中白细胞介素-10（IL-10）水平升高（6.7±0.4μg/ml）。与未手术的DBA/2J小鼠相比，脾切除的DBA/2J小鼠血浆中IL-10水平也有类似升高，但在C57BL/6J和BALB/cJ小鼠中未出现。相反，脾切除的AKR小鼠IL-10水平低于未手术小鼠。与假手术或未手术的A/J小鼠的PMphi相比，脾切除的A/J小鼠的PMphi产生的IL-10水平升高，这与体内观察结果相似。
我们的数据表明，脾脏在调节LPS诱导的炎症过程中起重要作用，这一作用超出了对包膜菌的被动清除。此外，脾脏对炎症过程的贡献可能受遗传背景影响。
