Treatment of Rheumatoid Arthritis-Marine/Botanical Oils

类风湿关节炎的治疗-海洋/植物油

• 批准号: 7618339
• 负责人: ROBERT B ZURIER
• 金额: $ 1.35万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7618339
• 关键词: Acids; Activities of Daily Living; Aftercare; American; Animals; Anti-Inflammatory Agents; Antigens; Arachidonic Acids; Awareness; Biochemical; Biological; Borago; Botanicals; Cells; Class; Clinical; Clinical Treatment; Clinical Trials; Corn Oil; Disease; Disease Progression; Docosahexaenoic Acids; Eicosanoids; Eicosapentaenoic Acid; Event; Fatty Acids; Film; Fish Oils; Gene Expression; Generations; Glutathione; Hand; Immune response; In Vitro; Inflammation; Inflammation Mediators; Inflammatory; Injury; Interleukin-1; Interleukins; Joints; Lead; Leukocytes; Lipoxygenase; Lymphoid; Lymphokines; Marines; Masks; Measures; Membrane Lipids; Methods; Mitogens; Molecular; Multi-Institutional Clinical Trial; Oils; Omega-3 Fatty Acids; Outcome; Outcome Measure; Patients; Phase; Placebos; Polyunsaturated Fatty Acids; Population; Production; Property; Prostaglandin-Endoperoxide Synthase; Reactive Oxygen Species; Recovery; Rheumatoid Arthritis; Rheumatology; Score; Seeds; Signal Transduction; Sulfhydryl Compounds; Surface; T-Cell Proliferation; T-Lymphocyte; Therapeutic Effect; Tissues; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; Unsaturated Fatty Acids; anakinra; base; borage oil; college; cyclooxygenase 1; cyclooxygenase 2; cytokine; foot; human TNF protein; lymphocyte proliferation; monocyte; oxidation; placebo controlled study; polypeptide; response

The object of this proposal is to determine whether treatment of rheumatoid arthritis (RA) with a combination of fish oil and borage seed oil is superior to treatment with either oil alone. Fish oil is rich in the antiinflammatory n3 unsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and borage oil contains gammalinolenic acid (GLA), an n6 unsaturated fatty acid with antiinflammatory and immunomodulatory properties. Administration of borage oil and offish oil both suppress the clinical manifestations of RA. Animal studies indicate that the mechanisms whereby fish oil suppresses inflammation are both similar to and different from the means by which GLA reduces inflammation and that the combination treatment is more effective than each treatment alone. This proposal is for a multi-center, two year, phase 3, double-masked, placebo-controlled trial of 375 patients, which includes 4 treatment groups: 1) corn oil as a polyunsaturated fatty acid control; 2) fish oil; 3) borage oil; 4) fish oil plus borage oil. Radiographic analysis (Sharp Scores) of hands and feet will be done at baseline, 12, and 24 months. Biochemical and molecular mechanisms whereby the fatty acid treatments influence activation of monocytes (cytokine and oxygen radical generation), and T lymphocytes (proliferation, cytokine production, Thl/Th2 skewing, signaling events) will be investigated. Results of the cell activation (ex vivo) studies will be correlated with clinical outcomes. Results of these studies should raise awareness of the usefulness of naturally occurring oils in inflammatory diseases, lead to more rational use of fatty acids in treatment of inflammatory arthritis, and provide a greater understanding of the mechanisms of action of antiinflammatory fatty acids.

本建议的目的是确定是否治疗类风湿性关节炎（RA）与 鱼油和琉璃苣籽油的组合上级单独使用任一种油的处理。鱼油是 富含1，3-不饱和脂肪酸二十碳五烯酸（EPA）， 二十二碳六烯酸（DHA），琉璃苣油含有γ-亚麻酸（GLA），一种n6 不饱和脂肪酸，具有降血脂和免疫调节特性。总局 琉璃苣油和鱼油都抑制RA的临床表现。动物研究表明 鱼油抑制炎症的机制既类似于又不同于 GLA减少炎症的方式，以及联合治疗更有效， 比单独治疗更有效。 本提案是一项多中心、2年、3期、双盲、安慰剂对照试验， 375例患者，其中包括4个治疗组：1）玉米油作为多不饱和脂肪酸对照; 2)鱼油; 3）琉璃苣油; 4）鱼油加琉璃苣油。影像学分析（Sharp评分） 将在基线、12个月和24个月时进行手和脚的检查。生化和分子 脂肪酸处理影响单核细胞活化的机制（细胞因子和 氧自由基产生）和T淋巴细胞（增殖、细胞因子产生、Th 1/Th 2 偏斜、信令事件）将被研究。细胞活化（离体）研究的结果将 与临床结果相关。 这些研究的结果应该提高人们对天然油脂在食品中的作用的认识。 炎症性疾病，导致更合理地使用脂肪酸治疗炎性关节炎， 并提供了更好的了解的机制，行动的脂肪酸。

项目成果

CD4+CD25high T cell numbers are enriched in the peripheral blood of patients with rheumatoid arthritis.

• DOI: 10.1016/j.cellimm.2008.05.007
• 发表时间: 2008-05
• 期刊: CELLULAR IMMUNOLOGY
• 影响因子: 4.3
• 作者: Han, Guang Ming;O'Neil-Andersen, Nancy J.;Zurier, Robert B.;Lawrence, David A.
• 通讯作者: Lawrence, David A.