Sleep Fragmentation Effects on Murine CII-Induced AR

描述(由申请人提供)： 类风湿性关节炎(RA)和其他慢性关节炎患者有部分慢性睡眠剥夺(PCSD)，可能与他们的病情相关的疼痛和炎症有关。目前尚不清楚PCSD对RA及相关关节炎的免疫和非免疫介导的关节炎过程有何影响。最近在实验室动物和人类中的研究表明，睡眠不足会产生与免疫相关的后果。本研究的总体目标是在DBA/1lac小鼠的初级免疫共振向卵蛋白(OVA)的进化过程中以及在同一品系的II型胶原(CII)诱导的关节炎(CIA)的进化过程中，诱导DBA/1lac小鼠的慢性部分睡眠碎裂。我们将测试这一假设，即DBA/1lac小鼠的PCSD将导致对OVA的免疫反应和关节炎严重程度的改变。该方法将量身定做适合小鼠的实验性慢性睡眠剥夺装置，开发和验证计算机化程序，以一致和可靠的方式实施选择性部分睡眠剥夺的实验条件，然后评估PCSD对CII免疫诱导的OVA和关节炎免疫反应的影响。以下特定目的将针对这一假设：特定目的1：评估关节炎小鼠的睡眠模式；特定目的2：对小鼠进行完全睡眠剥夺以产生部分睡眠剥夺的小鼠；特定目标3：确定OVA免疫的慢性部分睡眠剥夺DBA/1lac小鼠对OVA的免疫力是否发生改变；以及特定目标4：确定以CII免疫的慢性部分睡眠剥夺DBA/1lac小鼠的关节炎发病率和/或严重程度是否发生改变。这项研究的结果将为提交R01拨款提供基础，以探索DBA/1lac小鼠部分睡眠剥夺改变对抗原和关节炎发展的免疫反应的机制。

DESCRIPTION (provided by applicant): Patients with rheumatoid arthritis (RA) and other chronic arthritides have partial chronic sleep deprivation (PCSD) possibly related to the pain and inflammation associated with their condition. It is unknown what effect PCSD has on the immune and non-immune mediated arthritic processes of RA and related arthritides. Recent work in laboratory animals and humans indicates that sleep deprivation produces immune-related consequences. The overall goal of this study is to induce chronic, partial sleep fragmentation in DBA/1 lac mice during the evolution of the primary immune resonse to ovalbumin (OVA) in mice and during the evolution of type II collagen (CII)-induced arthritis (CIA) in this same mouse strain. We will test the hypothesis that PCSD in DBA/1 lac mice will result in alterations in the immune response to OVA and severity of arthritis. The approach will Ibe to tailor an experimental chronic sleep deprivation appartus to fit the mouse, develop and lvalidate a computerized program, implement experimental conditions of selective partial sleep Ideprivation in a consistent and reliable manner, and then assess the effects of PCSD on immune Iresponse to OVA and arthritis induced by immunization with CII. The following specific aims will address this hypothesis: Specific Aim 1: Assess sleep patterns in arthritic mice; Specific Aim 2: Conduct total sleep deprivation in mice to produce partially sleep-deprived mice; Specific Aim 3: Determine whether chronic partial sleep deprived DBA/1 lac mice immunized with OVA develop altered immunity to OVA; and Specific Aim 4: Determine whether chronic partial sleep-deprived DBA/1 lac mice immunized with CII have alterations in the incidence and/or severity of arthritis. Results of the study will provide a basis for submitting an R01 grant to explore mechanisms by which partial sleep deprivation in DBA/1 lac mice alter the immune response to antigen and arthritis development.