Arend W P, Guthridge C J
Division of Rheumatology, University of Colorado Health Sciences Center, Denver, 4200 East Ninth Avenue, Denver, CO 80262, USA.
Ann Rheum Dis. 2000 Nov;59 Suppl 1(Suppl 1):i60-4. doi: 10.1136/ard.59.suppl_1.i60.
The interleukin 1 receptor antagonist (IL1Ra) family of molecules now includes one secreted isoform (sIL1Ra) and three intracellular isoforms (icIL1Ra1, 2, and 3). Extensive evidence indicates that the sole biological function of sIL1Ra seems to be to competitively inhibit IL1 binding to cell-surface receptors. Although intracellular IL1Ra1 may be released from keratinocytes under some conditions, the intracellular isoforms of IL1Ra may carry out additional as yet poorly defined roles inside cells. Maintenance of a balance between IL1 and IL1Ra is important in preventing the development or progression of inflammatory disease in certain organs. Both the secreted and intracellular isoforms of IL1Ra contribute to maintenance of this balance. An allelic polymorphism in intron 2 of the IL1Ra gene (IL1RN*2) predisposes to the development or severity of a variety of human diseases largely of epithelial cell origin. Both the impaired production of IL1Ra and the overproduction of IL1beta are related to the presence of this allele. Restoration of the balance between IL1Ra and IL1 through a variety of approaches is a therapeutic goal in specific chronic inflammatory diseases.
白细胞介素1受体拮抗剂（IL1Ra）分子家族目前包括一种分泌型异构体（sIL1Ra）和三种细胞内异构体（icIL1Ra1、2和3）。大量证据表明，sIL1Ra的唯一生物学功能似乎是竞争性抑制IL1与细胞表面受体的结合。尽管细胞内IL1Ra1在某些情况下可能从角质形成细胞中释放出来，但IL1Ra的细胞内异构体可能在细胞内发挥其他尚未明确的作用。维持IL1和IL1Ra之间的平衡对于预防某些器官炎症性疾病的发生或进展很重要。IL1Ra的分泌型和细胞内异构体都有助于维持这种平衡。IL1Ra基因第2内含子中的一个等位基因多态性（IL1RN*2）易导致多种主要起源于上皮细胞的人类疾病的发生或严重程度增加。IL1Ra产生受损和IL1β过度产生均与该等位基因的存在有关。通过多种方法恢复IL1Ra和IL1之间的平衡是特定慢性炎症性疾病的治疗目标。
