INTERLEUKIN-1 (IL-1) GENE-EXPRESSION, SYNTHESIS, AND EFFECT OF SPECIFIC IL-1 RECEPTOR BLOCKADE IN RABBIT IMMUNE-COMPLEX COLITIS
INTERLEUKIN-1 (IL-1) GENE-EXPRESSION, SYNTHESIS, AND EFFECT OF SPECIFIC IL-1 RECEPTOR BLOCKADE IN RABBIT IMMUNE-COMPLEX COLITIS
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DOI：
10.1172/jci114799
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发表时间：
1990-09-01
影响因子：
15.9
通讯作者：
DINARELLO, CA
中科院分区：
文献类型：
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作者：
COMINELLI, F;NAST, CC;DINARELLO, CA
白细胞介素1 （IL-1）可能是炎症性肠病（IBD）炎症和组织损伤的关键介质。在兔免疫复合物诱导的结肠炎中，il -1。和度量。在结肠炎诱导后的第4小时可检测到mRNA水平，在第12小时达到峰值，但在第96小时不存在mRNA水平。用特异性放射免疫法测定结肠IL-1组织水平。il - 1. -α。在4 h时显著升高(9.4 +-。1.5 ng/g结肠)，48 h逐渐增加(31 .+-。5.8 ng/g)，然后下降96 h(11.5 +-。3.4 ng / g)。il - 1. - beta。水平为2.0 .+-。0.5 ng/g结肠在4小时，5.0 .+-。相比之下，PGE2和LTB4的结肠水平在前12小时内没有变化，直到24小时才升高。与炎症（r = 0.885, P < 0.0001）、水肿（r = 0.789, P < 0.0001）、坏死（r = 0.752, P < 0.0005）高度相关。特异性IL-1受体拮抗剂（IL-1ra）在给予免疫复合物之前和之后的前33小时内显著降低炎症细胞浸润指数(从3.2。0.4 ~ 1.4 .+-。0.3, P < 0.02)，水肿(从2.2。0.4到0.6 .+-。0.3, P < 0.01)和坏死(从43。10%到6.6 .+-。3.2%, P < 0.03)。这些研究表明(a) IL-1基因的表达和合成发生在免疫复合物诱导的结肠炎过程的早期；(b) PGE2和LTB4出现前12 h显著升高；(c)组织中IL-1水平与组织炎症程度相关；(3)特异性阻断IL-1受体可减少实验性结肠炎相关的炎症反应。
Interleukin 1 (IL-1) may be a key mediator of inflammation and tissue damage in inflammatory bowel disease (IBD). In rabbits with immune complex-induced colitis, IL-1.alpha. and .beta. mRNA levels were detectable at 4 h, peaked at 12 but were absent at 96 h after the induction of colitis. Colonic IL-1 tissue levels were measured by specific radioimmunoassays. IL-1.alpha. was significantly elevated at 4 h (9.4 .+-. 1.5 ng/g colon), progressively increased at 48 h (31 .+-. 5.8 ng/g) and then decreased by 96 h (11.5 .+-. 3.4 ng/g). IL-1.beta. levels were 2.0 .+-. 0.5 ng/g colon at 4 h, 5.0 .+-. 1.6 ng/g at 48 h and undetectable by 96 h. By comparison, colonic levels of PGE2 and LTB4 were unchanged during the first 12 h and did not become elevated until 24 h. IL-1.alpha. levels were highly correlated with inflammation (r = 0.885, P < 0.0001), edema (r = 0.789, P < 0.0001) and necrosis (r = 0.752, P < 0.0005). Treatment with a specific IL-1 receptor antagonist (IL-1ra) before and during the first 33 h after the administration of immune complexes markedly reduced inflammatory cell infiltration index (from 3.2 .+-. 0.4 to 1.4 .+-. 0.3, P < 0.02), edema (from 2.2 .+-. 0.4 to 0.6 .+-. 0.3, P < 0.01) and necrosis (from 43 .+-. 10% to 6.6 .+-. 3.2%, P < 0.03) compared to vehicle-matched colitis animals. These studies demonstrate that (a) IL-1 gene expression and synthesis occur early in the course of immune complex-induced colitis; (b) are significantly elevated for 12 h before the appearance of PGE2 and LTB4; (c) tissue levels of IL-1 correlate with the degree of tissue inflammation and; (3) specific blockade of IL-1 receptors reduces the inflammatory responses associated with experimental colitis.