Department of Academic Rheumatology, Centre for Molecular and Cellular Biology of Inflammation, 1st Floor New Hunts House, Guy's Campus, King's College London, London SE 1UL, UK.
Rheumatology (Oxford). 2012 May;51(5):780-8. doi: 10.1093/rheumatology/ker412. Epub 2011 Dec 20.
Appropriate regulation and subsequent resolution of acute inflammatory events is critical to the prevention of autoinflammatory diseases. Indeed, the chronic inflammation observed in diseases such as RA is at least partially consequent on the failure of endogenous immunoregulation. Current RA therapies (e.g. anti-TNF-α inhibitors and MTX) inhibit components of the inflammatory disease process without directly promoting the resolution of inflammation. We propose that the next generation of RA therapeutics will complement and augment endogenous immunoregulatory and pro-resolution immunological networks, thus promoting the definitive resolution of inflammation rather than temporary immunological control. Of particular interest with respect to this therapeutic approach is binding immunoglobulin protein [BiP; also known as glucose-regulated protein-78 (GRP78)], a member of the recently defined resolution-associated molecular pattern (RAMP) family of molecules. In this review, we consider the preclinical evidence from experiments in mouse and man that suggests BiP and other members of the RAMP family have the potential to herald a new generation of immunotherapeutics.
适当的调节和随后的急性炎症事件的解决对于预防自身炎症性疾病至关重要。事实上，在 RA 等疾病中观察到的慢性炎症至少部分是由于内源性免疫调节失败所致。目前的 RA 治疗方法（例如抗 TNF-α 抑制剂和 MTX）抑制炎症疾病过程的成分，而不会直接促进炎症的解决。我们提出，下一代 RA 治疗方法将补充和增强内源性免疫调节和促解决免疫网络，从而促进炎症的明确解决，而不是暂时的免疫控制。关于这种治疗方法，特别有趣的是结合免疫球蛋白蛋白 [BiP；也称为葡萄糖调节蛋白-78 (GRP78)]，它是最近定义的解决相关分子模式 (RAMP) 分子家族的成员。在这篇综述中，我们考虑了来自小鼠和人类实验的临床前证据，这些证据表明 BiP 和 RAMP 家族的其他成员有可能预示着新一代免疫疗法的出现。
