An expanding role for interleukin-1 blockade from gout to cancer.
An expanding role for interleukin-1 blockade from gout to cancer.
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DOI：
10.2119/molmed.2014.00232
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发表时间：
2014-12-16
期刊：
影响因子：
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通讯作者：
Dinarello, Charles Anthony
中科院分区：
文献类型：
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作者：
Dinarello, Charles Anthony
白细胞介素(IL)-1在痛风和癌症等疾病中的作用越来越大。与任何其他细胞因子家族相比，IL-1家族与先天炎症和免疫反应密切相关。这是因为所有IL-1受体家族成员的细胞质片段都包含一个结构域，该结构域与所有toll样受体（TLRs）的细胞质结构域高度同源。这个结构域被称为“toll IL-1受体（TIR）结构域”，与IL-1受体一样发出信号；因此，由TLR和IL-1家族引起的炎症几乎相同。如环加氧酶2型的诱导、细胞粘附分子表面表达的增加和大量炎症分子基因表达的增加等基本反应是IL-1信号转导的特征，就像它对TLR激动剂一样。IL-1 β是IL-1家族中研究最多的成员，因为它在介导自身炎症性疾病中起作用。然而，il -1 α在疾病中的作用正在被验证，因为一种针对人il -1 α的中和单克隆抗体的可用性。目前有三种被批准的阻断IL-1活性的疗法。Anakinra是天然存在的IL-1受体拮抗剂的重组形式，它与IL-1受体结合并阻止IL-1 β和IL-1 α的结合。Rilonacept是一种可溶性诱骗受体，主要中和il -1 β，但也中和il -1 α。Canakinumab是一种仅中和il -1 β的人单克隆抗体。因此，可以确定il -1 β和il -1 α在人类疾病中的因果关系或重要贡献作用。
There is an expanding role for interleukin (IL)-1 in diseases from gout to cancer. More than any other cytokine family, the IL-1 family is closely linked to innate inflammatory and immune responses. This linkage is because the cytoplasmic segment of all members of the IL-1 family of receptors contains a domain, which is highly homologous to the cytoplasmic domains of all toll-like receptors (TLRs). This domain, termed "toll IL-1 receptor (TIR) domain," signals as does the IL-1 receptors; therefore, inflammation due to the TLR and the IL-1 families is nearly the same. Fundamental responses such as the induction of cyclo-oxygenase type 2, increased surface expression of cellular adhesion molecules and increased gene expression of a broad number of inflammatory molecules characterizes IL-1 signal transduction as it does for TLR agonists. IL-1beta is the most studied member of the IL-1 family because of its role in mediating autoinflammatory disease. However, a role for IL-1alpha in disease is being validated because of the availability of a neutralizing monoclonal antibody to human IL-1alpha. There are presently three approved therapies for blocking IL-1 activity. Anakinra is a recombinant form of the naturally occurring IL-1 receptor antagonist, which binds to the IL-1 receptor and prevents the binding of IL-1beta as well as IL-1alpha. Rilonacept is a soluble decoy receptor that neutralizes primarily IL-1beta but also IL-1alpha. Canakinumab is a human monoclonal antibody that neutralizes only IL-1beta. Thus, a causal or significant contributing role can be established for IL-1beta and IL-1alpha in human disease.