Wong Peter K K, Campbell Ian K, Robb Lorraine, Wicks Ian P
Reid Rheumatology Laboratory, Division of Autoimmunity and Transplantation, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
Cytokine. 2005 Jan 21;29(2):72-6. doi: 10.1016/j.cyto.2004.09.011.
To evaluate the role of interleukin-11 (IL-11) in acute mBSA/IL-1-induced inflammatory arthritis.
IL-11 was administered via intra-articular (IA) injection into knee joints of C57BL/6 mice and joint histology was assessed. The mitogenic response to IL-11 was measured in wild-type (WT) synovial fibroblasts. IL-1 was used as a comparator in both the studies. The severity of acute methylated bovine serum albumin (mBSA)/IL-1 arthritis was determined in WT and IL-11 receptor null (IL-11Ra1-/-) mice. In parallel experiments, a neutralising antibody to IL-11 was administered to WT mice throughout this model.
IA injections of IL-11 resulted in mild-to-moderate joint inflammation which was less than that due to IA IL-1. IL-11 had a dose-dependent mitogenic effect on WT synovial fibroblasts (P<0.01). mBSA/IL-1 acute arthritis was reduced in IL-11Ra1-/- versus WT mice (histological arthritis score: 10.1+/-0.5 versus 12.8+/-0.7, respectively; P=0.01). Administration of an IL-11 neutralising antibody to WT mice reduced mBSA/IL-1 acute arthritis scores compared to control antibody (10.6+/-0.7 versus 13.3+/-0.6, respectively; P=0.02).
These data demonstrate that endogenous IL-11 exerts relatively mild but consistent pro-inflammatory effects in acute inflammatory arthritis.
评估白细胞介素-11(IL-11)在急性甲基化牛血清白蛋白(mBSA)/IL-1诱导的炎性关节炎中的作用。
通过关节内(IA)注射将IL-11注入C57BL/6小鼠的膝关节,并评估关节组织学。在野生型(WT)滑膜成纤维细胞中测量对IL-11的促有丝分裂反应。在两项研究中均将IL-1用作对照。在WT和IL-11受体缺失(IL-11Ra1-/-)小鼠中确定急性甲基化牛血清白蛋白(mBSA)/IL-1关节炎的严重程度。在平行实验中,在整个模型中对WT小鼠施用抗IL-11中和抗体。
IA注射IL-11导致轻度至中度关节炎症,低于IA注射IL-1所引起的炎症。IL-11对WT滑膜成纤维细胞具有剂量依赖性促有丝分裂作用(P<0.01)。与WT小鼠相比,IL-11Ra1-/-小鼠的mBSA/IL-1急性关节炎减轻(组织学关节炎评分分别为10.1±0.5和12.8±0.7;P=0.01)。与对照抗体相比,对WT小鼠施用IL-11中和抗体可降低mBSA/IL-1急性关节炎评分(分别为10.6±0.7和13.3±0.6;P=0.02)。
这些数据表明内源性IL-11在急性炎性关节炎中发挥相对轻微但持续存在的促炎作用。