Despite the existence of potent anti-inflammatory biological drugs e.g., anti-TNF and anti IL-6 receptor antibodies, for treating chronic inflammatory and autoimmune diseases, these are costly and not specific. Cheaper oral available drugs remain an unmet need. Expression of the acute phase protein Serum Amyloid A (SAA) is dependent on release of pro-inflammatory cytokines IL-1, IL-6 and TNF-α during inflammation. Conversely, SAA induces pro-inflammatory cytokine secretion, including Th17, leading to a pathogenic vicious cycle and chronic inflammation. 5- MER peptide (5-MP) MTADV (methionine-threonine-alanine-aspartic acid-valine), also called Amilo-5MER, was originally derived from a sequence of a pro-inflammatory CD44 variant isolated from synovial fluid of a Rheumatoid Arthritis (RA) patient. This human peptide displays an efficient anti-inflammatory effects to ameliorate pathology and clinical symptoms in mouse models of RA, Inflammatory Bowel Disease (IBD) and Multiple Sclerosis (MS). Bioinformatics and qRT-PCR revealed that 5-MP, administrated to encephalomyelytic mice, up-regulates genes contributing to chronic inflammation resistance. Mass spectrometry of proteins that were pulled down from an RA synovial cell extract with biotinylated 5-MP, showed that it binds SAA. 5-MP disrupted SAA assembly, which is correlated with its pro-inflammatory activity. The peptide MTADV (but not scrambled TMVAD) significantly inhibited the release of pro-inflammatory cytokines IL-6 and IL-1β from SAA-activated human fibroblasts, THP-1 monocytes and peripheral blood mononuclear cells. 5-MP suppresses the pro-inflammatory IL-6 release from SAA-activated cells, but not from non-activated cells. 5-MP could not display therapeutic activity in rats, which are SAA deficient, but does inhibit inflammations in animal models of IBD and MS, both are SAA-dependent, as shown by others in SAA knockout mice. In conclusion, 5-MP suppresses chronic inflammation in animal models of RA, IBD and MS, which are SAA-dependent, but not in animal models, which are SAA-independent.

尽管存在用于治疗慢性炎症和自身免疫疾病的强效抗炎生物药物，例如抗TNF和抗IL-6受体抗体，但这些药物成本高且没有特异性。更便宜的口服药物仍然是一个未满足的需求。急性期蛋白血清淀粉样蛋白 A (SAA) 的表达依赖于炎症期间促炎细胞因子 IL-1、IL-6 和 TNF-α 的释放。相反，SAA 诱导促炎细胞因子分泌，包括 Th17，导致致病恶性循环和慢性炎症。5-MER 肽 (5-MP) MTADV（蛋氨酸-苏氨酸-丙氨酸-天冬氨酸-缬氨酸），也称为 Amilo-5MER，最初来源于从类风湿性关节炎的滑液中分离的促炎 CD44 变体序列(RA) 患者。这种人类肽显示出有效的抗炎作用，可改善 RA、炎症性肠病 (IBD) 和多发性硬化症 (MS) 小鼠模型的病理和临床症状。生物信息学和 qRT-PCR 显示，给予脑脊髓炎小鼠的 5-MP 上调导致慢性炎症抗性的基因。用生物素化的 5-MP 从 RA 滑膜细胞提取物中提取的蛋白质的质谱分析表明，它与 SAA 结合。5-MP 破坏了 SAA 组装，这与其促炎活性相关。肽 MTADV（但不是乱序的 TMVAD）显着抑制 SAA 激活的人成纤维细胞、THP-1 单核细胞和外周血单核细胞释放促炎细胞因子 IL-6 和 IL-1β。5-MP 抑制 SAA 活化细胞释放促炎性 IL-6，但不抑制非活化细胞释放。5-MP 不能在缺乏 SAA 的大鼠中显示治疗活性，但在 IBD 和 MS 的动物模型中确实抑制炎症，两者都是 SAA 依赖性的，如 SAA 敲除小鼠中的其他人所示。总之，5-MP 在依赖 SAA 的 RA、IBD 和 MS 动物模型中抑制慢性炎症，但在不依赖 SAA 的动物模型中不抑制慢性炎症。