Zimmerman Michael A, Reznikov Leonid L, Raeburn Christopher D, Selzman Craig H
Department of Surgery, University of Colorado Health, Sciences Center, Denver, Colorado, USA.
J Surg Res. 2004 Oct;121(2):206-13. doi: 10.1016/j.jss.2004.03.025.
The inflammatory response to vascular injury is characterized by expression of cytokines, growth factors, and chemokines that conspire to promote vessel remodeling and intimal hyperplasia (IH). Interleukin-10 (IL-10) is a multifunctional cytokine that has several anti-inflammatory properties in vitro. Few studies have evaluated the effects of IL-10 in experimental atherosclerosis. The purpose of the present study was to determine the influence of IL-10 on vascular inflammation and IH following mechanical injury.
Wire carotid injury was performed in wild-type (WT) mice with and without IL-10 treatment. Immunohistochemistry, PCR, and ELISA assays were used to examine vessel production of basic fibroblast growth factor (bFGF), monocyte chemotactic protein-1 (MCP-1), and nuclear factor kappa B (NFkappaB). Vessels were morphometrically analyzed for IH.
Carotid injury induced early expression of MCP-1 and bFGF that was abrogated in mice treated with IL-10. Similarly, injury-induced expression of NFkappaB message and protein was attenuated in mice receiving exogenous IL-10. Compared to untreated mice, IL-10 markedly decreased levels of IH. Interestingly, carotid injury in IL-10-deficient mice resulted in an augmented IH response compared to injured WT mice.
In an in vivo model of direct vascular injury, IL-10 decreased expression of the pro-inflammatory transcription factor, NFkappaB, and the mitogenic chemokine and growth factor, MCP-1 and bFGF, respectively. These observations were associated with IL-10-induced attenuation of IH. Furthermore, endogenous IL-10 appeared to suppress the injury response. In conclusion, exogenously delivered IL-10 may represent a clinically relevant anti-inflammatory strategy for post-injury intimal hyperplasia.
对血管损伤的炎症反应的特征是细胞因子、生长因子和趋化因子的表达，这些因子共同促进血管重塑和内膜增生（IH）。白细胞介素-10（IL-10）是一种多功能细胞因子，在体外具有多种抗炎特性。很少有研究评估IL-10在实验性动脉粥样硬化中的作用。本研究的目的是确定IL-10对机械损伤后血管炎症和内膜增生的影响。
对野生型（WT）小鼠进行颈动脉钢丝损伤，部分小鼠接受IL-10治疗。采用免疫组织化学、聚合酶链反应（PCR）和酶联免疫吸附测定（ELISA）检测血管中碱性成纤维细胞生长因子（bFGF）、单核细胞趋化蛋白-1（MCP-1）和核因子κB（NFκB）的产生。对血管进行形态计量分析以评估内膜增生情况。
颈动脉损伤诱导MCP-1和bFGF的早期表达，而在用IL-10治疗的小鼠中这种表达被消除。同样，在接受外源性IL-10的小鼠中，损伤诱导的NFκB信使核糖核酸和蛋白表达减弱。与未治疗的小鼠相比，IL-10显著降低了内膜增生水平。有趣的是，与受伤的WT小鼠相比，IL-10基因缺陷小鼠的颈动脉损伤导致内膜增生反应增强。
在直接血管损伤的体内模型中，IL-10分别降低了促炎转录因子NFκB以及促有丝分裂趋化因子和生长因子MCP-1和bFGF的表达。这些观察结果与IL-10诱导的内膜增生减弱有关。此外，内源性IL-10似乎抑制了损伤反应。总之，外源性给予IL-10可能代表一种针对损伤后内膜增生的具有临床相关性的抗炎策略。
