INTERLEUKIN-1 SUPPRESSES INFLAMMATION IN RABBIT COLITIS - MEDIATION BY ENDOGENOUS PROSTAGLANDINS
INTERLEUKIN-1 SUPPRESSES INFLAMMATION IN RABBIT COLITIS - MEDIATION BY ENDOGENOUS PROSTAGLANDINS
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DOI：
10.1172/jci114476
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发表时间：
1990-02-01
影响因子：
15.9
通讯作者：
ZIPSER, RD
中科院分区：
文献类型：
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作者：
COMINELLI, F;NAST, CC;ZIPSER, RD
低剂量IL-1预处理在炎症或组织损伤的动物模型中具有保护作用，但这些保护作用的机制尚未建立。为了确定是否涉及白藜芦醇，我们施用了人重组IL-1 β。并测量了患有福尔马林免疫复合物结肠炎的兔子的直肠PGE 2产生。IL-1.beta. (0.3在诱导结肠炎前24小时给药的PGE 2（231 ± 0.01 μ g/kg）增加了PGE 2（231 ± 0.01 μ g/kg）。36比1,299 +-。572 pg/ml，P < 0.01）和降低随后的炎性细胞浸润指数（从2.8 ± 0.01）。0.3至1.4 .+-。0.3，P < 0.02）和水肿（从2.5 ± 0.01）。0.3至1.3 .+-。0.3，P < 0.01）。给予布洛芬（10 mg/kg i. v.）以及IL-1 β。阻止了PGE 2的刺激和炎症的减少。结肠PGE 2的产生与炎症（P < 0.02，r = -0.39）和水肿（P < 0.04，r = -0.35）的严重程度呈负相关。诱导结肠炎前30分钟给予IL-1并不影响炎症的严重程度。类似地，用人IL-1 β的非炎性合成肽（片段163-171）预处理，在结肠炎诱导前30分钟或24小时，没有减轻炎症或增加前列腺素合成。这些数据表明用IL-1 β预处理诱导结肠炎前24小时通过需要前列腺素合成的机制减少炎症。
Pretreatment with low-dose IL-1 has protective effects in animal models of inflammation or tissue injury, but the mechanisms of these protective effects are not established. To determine if prostaglandins are involved, we administered human recombinant IL-1.beta. and measured rectal PGE2 production in rabbits with formalin-immune complex colitis. IL-1.beta. (0.3 .mu.g/kg) administered 24 h before induction of colitis increased PGE2 (231 .+-. 36 to 1,299 .+-. 572 pg/ml, P < 0.01) and reduced subsequent inflammatory cell infiltration index (from 2.8 .+-. 0.3 to 1.4 .+-. 0.3, P < 0.02) and edema (from 2.5 .+-. 0.3 to 1.3 .+-. 0.3, P < 0.01) compared with vehicle-matched animals. Administration of ibuprofen (10 mg/kg i.v.) together with IL-1.beta. prevented the stimulation of PGE2 and the reduction in inflammation. Colonic PGE2 production correlated inversely with susequent severity of inflammation (P < 0.02, r = -0.39) and edema (P < 0.04, r = -0.35). IL-1-administration 30 min before induction of colitis did not affect the severity of inflammation. Similarly, pretreatment with a noninflammatory synthetic peptide (fragment 163-171) of human IL-1.beta., either 30 min or 24 h before colitis induction, did not reduce inflammation or increase prostaglandin synthesis. These data demonstrate that pretreatment with IL-1.beta. 24 h before the induction of colitis reduces inflammation by a mechanism that requires prostaglandin synthesis.