The role of interferon gamma and nitric oxide as downregulating molecules in central nervous system inflammation

干扰素γ和一氧化氮作为下调分子在中枢神经系统炎症中的作用

• 批准号: nhmrc : 127600
• 负责人: David Willenborg
• 金额: $ 35.12万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2000
• 资助国家: 澳大利亚
• 起止时间: 2000-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/role-interferon-gamma-nervous-inflammation/82225
• 关键词: role; interferon; gamma; nitric; oxide

Cytokines are soluble factors which participate in inflammatory responses. Interferon gamma is a cytokine which in the context of central nervous system inflammation has been considered a Obad? molecule, as has the gas nitric oxide which is induced by interferon gamma. We now have direct evidence that indicate quite the contrary, ie interferon gamma and nitric oxide can a do act as down regulators of inflammation. The present work is designed to determine if this down regulating function is restricted only to a single model of CNS inflammation or is a general phenomenon within the CNS. The project will also involve a number of experiments designed to elucidate the mechanism(s) by which down regulation occurs. This project is highly significant in that a single uncontrolled clinical trial of interferon gamma for the therapy of MS has been carried out and reported as indicating that interferon gamma made the disease worse. The design of that trial however was such that the validity of that claim is questionable. If our experiments confirm the general nature of interferon gamma as a down regulator in inflammation in a number of different models of MS then a case for revisiting the use of interferon, or a downstream product of interferon, in the therapy of MS might be made.

细胞因子是参与炎症反应的可溶性因子。干扰素是一种细胞因子，在中枢神经系统炎症的背景下一直被认为是一种不良反应？分子，还有干扰素伽马诱导的一氧化氮气体。我们现在有直接证据表明恰恰相反，即干扰素伽马和一氧化氮确实可以作为炎症的降调因子。目前的工作旨在确定这种下调功能是仅限于单一的中枢神经系统炎症模型，还是中枢神经系统内的普遍现象。该项目还将包括一些旨在阐明下调调控发生机制的实验(S)。这一项目具有重要意义，因为已经进行了一项治疗多发性硬化症的干扰素伽玛临床试验，据报道，该试验表明干扰素伽玛使病情恶化。然而，该审判的设计使得这一说法的有效性值得怀疑。如果我们的实验证实了干扰素伽马在一些不同的MS模型中作为炎症下行调节因子的一般性质，那么就有可能重新探讨干扰素或干扰素的下游产品在MS治疗中的使用。