Pediatric Pneumology and Immunology, Charité University Medicine Berlin, Augustenburger Platz 1, 13353, Berlin, Germany,
Semin Immunopathol. 2015 Jul;37(4):429-37. doi: 10.1007/s00281-015-0501-9. Epub 2015 Jun 10.
In autoinflammatory disorders, dysregulation of the innate immune response leads to an excessive cytokine release. The disease course is often characterized by high morbidity and mortality, treatment is mostly difficult and therapeutic options are limited. In most cases, life-long control of ongoing inflammation is necessary in order to improve clinical symptoms and prevent development of damage. Steroids are helpful in many conditions, but the development of serious side effects often limits their long-term use. Other immunosuppressive, steroid-sparing medications are less effective than in the treatment of autoimmune diseases or do not show any effect. So far, anti-IL1α and/or β-blocking agents as well as an IL-6 receptor-blocking monoclonal antibody and, to a lesser extent, TNF-α blocking agents were applied in autoinflammatory disorders and significantly improved the outcome. Although these progresses were made in the last years, there are still numerous challenges in order to improve drug therapy in autoinflammation. This review summarizes the current state of new drug development and discusses advantages and disadvantages of possible targets.
在自身炎症性疾病中，先天免疫反应的失调导致细胞因子的过度释放。疾病过程通常具有高发病率和死亡率的特点，治疗大多困难，治疗选择有限。为了改善临床症状和预防损伤的发展，大多数情况下需要终身控制持续的炎症。在许多情况下，类固醇是有帮助的，但严重副作用的发展常常限制了它们的长期使用。其他免疫抑制、类固醇节约药物在治疗自身免疫性疾病时效果不如预期，或者没有效果。到目前为止，抗 IL1α 和/或β阻断剂以及 IL-6 受体阻断单克隆抗体，在一定程度上，TNF-α 阻断剂已应用于自身炎症性疾病，并显著改善了预后。尽管近年来取得了这些进展，但仍存在许多挑战，以改善自身炎症的药物治疗。本文综述了新药开发的现状，并讨论了可能的靶点的优缺点。
