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首页> 外文期刊>European Cells & Materials >Sustained intra-articular delivery of IL-1Ra from a thermally-responsive elastin-like polypeptide as a therapy for post-traumatic arthritis
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Sustained intra-articular delivery of IL-1Ra from a thermally-responsive elastin-like polypeptide as a therapy for post-traumatic arthritis

机译：从热反应性弹性蛋白样多肽持续关节内递送IL-1Ra作为创伤后关节炎的疗法

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Post-traumatic arthritis (PTA) is a rapidly progressive form of arthritis that develops due to joint injury, including articular fracture. Current treatments are limited to surgical restoration and stabilization of the joint; however, evidence suggests that PTA progression is mediated by the upregulation of pro-inflammatory cytokines, such as interleukin-1 (IL-1) or tumor necrosis factor-α (TNF-α). Although these cytokines provide potential therapeutic targets for PTA, intra-articular injections of anti-cytokine therapies have proven difficult due to rapid clearance from the joint space. In this study, we examined the ability of a cross-linked elastin-like polypeptide (xELP) drug depot to provide sustained intra-articular delivery of IL-1 and TNF-α inhibitors as a beneficial therapy. Mice sustained a closed intra-articular tibial plateau fracture; treatment groups received a single intra-articular injection of drug encapsulated in xELP. Arthritic changes were assessed 4 and 8 weeks after fracture. Inhibition of IL-1 significantly reduced the severity of cartilage degeneration and synovitis. Inhibition of TNF-α alone or with IL-1 led to deleterious effects in bone morphology, articular cartilage degeneration, and synovitis. These findings suggest that IL-1 plays a critical role in the pathogenesis of PTA following articular fracture, and sustained intra-articular cytokine inhibition may provide a therapeutic approach for reducing or preventing joint degeneration following trauma.
机译：创伤后关节炎（PTA）是关节炎的一种快速发展形式，由于关节损伤（包括关节骨折）而发展。目前的治疗仅限于外科手术修复和稳定关节。然而，有证据表明，PTA的进展是由促炎性细胞因子（如白介素-1（IL-1）或肿瘤坏死因子-α（TNF-α））的上调介导的。尽管这些细胞因子为PTA提供了潜在的治疗靶标，但由于从关节间隙快速清除，关节腔内注射抗细胞因子疗法已被证明是困难的。在这项研究中，我们检查了交联的弹性蛋白样多肽（xELP）药物仓库提供持续的IL-1和TNF-α抑制剂关节内递送作为有益治疗的能力。小鼠患有闭合的关节内胫骨平台骨折;治疗组接受关节腔内注射xELP封装的药物。骨折后4和8周评估关节炎的变化。 IL-1的抑制显着降低了软骨变性和滑膜炎的严重程度。单独或与IL-1一起抑制TNF-α会对骨骼形态，关节软骨变性和滑膜炎产生有害影响。这些发现表明，IL-1在关节骨折后PTA的发病机理中起着关键作用，持续的关节内细胞因子抑制可能为减少或预防创伤后关节变性提供治疗方法。

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