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LPS-induced knee-joint reactive arthritis and spinal cord glial activation were reduced after intrathecal thalidomide injection in rats.

机译:大鼠鞘内注射沙利度胺后,LPS诱发的膝关节反应性关节炎和脊髓神经胶质活化减少。

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AIMS: Thalidomide is thought to prevent TNF-alpha production, and such mechanism could be useful in a spinally delivered drug approach for the control of peripheral inflammation. This study aimed to evaluate the effect of intrathecal thalidomide, in comparison with that of intraperitoneal treatment, on articular incapacitation, edema, synovial leukocyte content, and spinal cord glial activation in a model of Escherichia coli lipopolysaccharide (LPS)-induced reactive arthritis in rats. MAIN METHODS: LPS (30ng) was injected into a knee-joint previously primed with carrageenan (300mug). Systemic (30 and 100mg/kg; intraperitoneal, i.p.) and intrathecal (10 and 100mug; i.t.) thalidomide were given 1h or 20min before LPS injection, respectively. Articular incapacitation and edema were evaluated hourly. After 6h, synovial fluid and lumbar spinal cords were collected for subsequent evaluations of cell migration and expression of CD11b/c and GFAP markers, respectively. KEY FINDINGS: Systemic (30 and 100mg/kg) or intrathecal (10 and 100mug) thalidomide reduced articular incapacitation, edema, and polymorphonuclear migration. In addition, i.p. and i.t. thalidomide reduced the expression of CD11b/c and GFAP markers in the lumbar spinal cord. These results suggest that thalidomide can also produce peripheral anti-inflammatory effects through action in the spinal cord that may involve glia inhibition. SIGNIFICANCE: This study provides new evidence that the direct spinal delivery of immunomodulators may be an alternative for the treatment of arthritic diseases, which require long systemic treatment with drugs associated with undesirable side effects.
机译:目的:沙利度胺被认为可以预防TNF-α的产生,这种机制在控制周围炎症的脊柱输送药物中可能有用。这项研究旨在评估鞘内注射沙利度胺与腹膜内治疗相比对大鼠脂多糖(LPS)诱发的反应性关节炎大鼠关节功能丧失,水肿,滑膜白细胞含量和脊髓神经胶质活化的影响。主要方法:将LPS(30ng)注入预先用角叉菜胶(300mug)灌注的膝关节中。注射LPS前1h或20min分别给予全身性(30和100mg / kg;腹膜内,腹膜内)和鞘内(10和100mug; i.t。)沙利度胺。每小时评估一次关节功能丧失和水肿。 6小时后,收集滑液和腰脊髓以分别评估细胞迁移以及CD11b / c和GFAP标志物的表达。主要发现:全身性(30和100mg / kg)或鞘内(10和100mug)沙利度胺减少了关节功能丧失,水肿和多形核迁移。另外,i.p。还有沙利度胺降低腰椎脊髓CD11b / c和GFAP标记的表达。这些结果表明,沙利度胺还可以通过可能牵涉神经胶质抑制的脊髓作用而产生外周抗炎作用。意义:这项研究提供了新的证据,表明免疫调节剂的直接脊柱输送可能是治疗关节炎疾病的一种替代方法,该疾病需要长期全身治疗,并需要与不良副作用相关的药物。

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