Maloff B L, Shaw J E, Di Meo T M
Medical Products Department, E. I. Du Pont de Nemours and Co., Inc., Wilmington, Delaware.
J Pharmacol Methods. 1989 Sep;22(2):133-40. doi: 10.1016/0160-5402(89)90042-9.
Interleukin-1 (IL-1) mediates a number of immunologic and physiologic responses associated with inflammation. A new model to monitor the primary effects of IL-1 and potential inhibitors on inflammation has been developed, which involves unilateral injection of 300 U of highly purified recombinant human IL-1 in mouse ears. Ear thickness of IL-1 injected ears increased 7-10-fold 24 hr posttreatment, concomitant with a corresponding increase in myeloperoxidase activity, suggesting that neutrophil influx contributes to this response. Administration of nonsteroidal antiinflammatory drugs did not influence the IL-1 effect in vivo. Inhibition of phospholipase A2 activity ameliorated the IL-1 stimulated inflammation; treatment with 10 mg/kg dexamethaxone eliminated approximately 80% of increased myeloperoxidase activity compared to control values. This model provides a well-defined in vivo assay with which to quantify the systemic effects of compounds capable of altering the activity of IL-1, and the data suggest that this mechanism may explain the unique efficacy of steroids as antiinflammatories.
白细胞介素 -1（IL-1）介导许多与炎症相关的免疫和生理反应。已开发出一种新模型来监测IL-1及其潜在抑制剂对炎症的主要作用，该模型涉及在小鼠耳部单侧注射300 U高纯度重组人IL-1。注射IL-1的耳部在治疗后24小时厚度增加7至10倍，同时髓过氧化物酶活性相应增加，这表明中性粒细胞流入促成了这种反应。给予非甾体抗炎药在体内不影响IL-1的作用。抑制磷脂酶A2活性可改善IL-1刺激的炎症；与对照值相比，用10 mg/kg地塞米松治疗可消除约80%的髓过氧化物酶活性增加。该模型提供了一种明确的体内测定方法，用以量化能够改变IL-1活性的化合物的全身作用，并且数据表明该机制可能解释了类固醇作为抗炎药的独特功效。
