Treatment of arthritis with interleukins

描述（由申请人提供）：该项目的总体目标是开发一种靶向递送IL-4到关节炎关节的治疗方法。类风湿性关节炎是一种以进行性软骨和骨侵蚀为特征的自身免疫性疾病。细胞因子是免疫反应的重要调节因子，IL-4是治疗关节炎的重要细胞因子。局部给药IL-4对中度关节炎患者有治疗作用。然而，由于其毒性，细胞因子的治疗效果受到限制。为了提高细胞因子的治疗效果，必须在不引起不良副作用的情况下增加其在疾病部位的浓度。所提出的方法抑制所给细胞因子的生物活性，直到其达到靶细胞的邻近。细胞因子随后变得活跃并在疾病部位集中。在关节炎关节内的细胞因子浓度可以达到预期的治疗效果而不产生全身毒性。这种靶向递送方法可适用于其他细胞因子和疾病，可作为其他治疗的辅助或单独使用。在第一阶段，我们将开发生物试剂并在体外进行测试。我们将在评估动物关节炎治疗的II期临床前研究中使用这些试剂。

DESCRIPTION (provided by applicant): The overall goal of this project is to develop a therapeutic method for targeted delivery of IL-4 to arthritic joints. Rheumatoid arthritis is an autoimmune disease characterized by progressive cartilage and bone erosion. Cytokines are important modulators of immune responses and IL-4 is an attractive cytokine for treating arthritis. Local administration of IL-4 has therapeutic effects in patients with moderate arthritis. However, the therapeutic efficacy of the cytokine is limited due to its toxicity. To improve the cytokine therapeutic effect, its concentration in a disease site has to be increased without causing undesirable side effects. The proposed method suppresses the biological activity of the administered cytokine until it reaches proximity of a target cell. The cytokine is then rendered active and concentrates in a disease site. The cytokine concentration in arthritic joints can reach levels that have desired therapeutic effects without systemic toxicity. This targeted delivery approach can be adapted for other cytokines and diseases and can be used as adjuvant to other treatments or stand alone. In Phase I we will develop the biological reagents and test them in vitro. We will use these reagents in Phase II in preclinical studies evaluating treatment of arthritis in animals.