Sims J E, Giri J G, Dower S K
Immunex Research and Development Corporation, Seattle, Washington 98101.
Clin Immunol Immunopathol. 1994 Jul;72(1):9-14. doi: 10.1006/clin.1994.1100.
The proinflammatory cytokine interleukin-1 binds to two cell-surface receptors. The type I receptor, an 80-kDa protein with a cytoplasmic domain of approximately 215 amino acids, mediates the biological effects of IL-1. The type II receptor, a 60-kDa protein with 29 cytoplasmic amino acids, binds IL-1 and thereby prevents it from binding to the type I receptor but does not deliver a biological signal. Thus, the type II receptor acts as a negative regulator of IL-1 actions. It can do so either as a membrane-bound molecule or subsequent to shedding from the cell surface to generate a so-called "soluble" receptor. Both the naturally produced soluble type II receptor and the recombinantly generated soluble type I receptor are effective inhibitors of IL-1 action. The soluble type I receptor has shown efficacy in some preclinical models of inflammatory diseases, as well as in an initial clinical trial in a setting of cutaneous allergy.
促炎细胞因子白细胞介素-1与两种细胞表面受体结合。I型受体是一种80 kDa的蛋白质，其胞质结构域约有215个氨基酸，介导IL-1的生物学效应。II型受体是一种60 kDa的蛋白质，有29个胞质氨基酸，可结合IL-1，从而阻止其与I型受体结合，但不传递生物学信号。因此，II型受体作为IL-1作用的负调节因子。它可以作为膜结合分子发挥作用，也可以在从细胞表面脱落以产生所谓的“可溶性”受体后发挥作用。天然产生的可溶性II型受体和重组产生的可溶性I型受体都是IL-1作用的有效抑制剂。可溶性I型受体在一些炎症性疾病的临床前模型中以及在皮肤过敏的初步临床试验中均显示出疗效。
