Conti P, Panara M R, Barbacane R C, Bongrazio M, Dempsey R A, Reale M
Immunology Division, University of Chieti Medical School, Italy.
Clin Exp Immunol. 1993 Mar;91(3):526-31. doi: 10.1111/j.1365-2249.1993.tb05936.x.
The effect of human recombinant IL-1 receptor antagonist (hrIL-1Ra) on leukotriene B4 (LTB4) release was investigated in activated human monocyte cultures. To stimulate LTB4 generation, LPS was used as an agonist. Detection was performed with the highly sensitive radioimmunoassay method. The cells were treated with scalar concentrations using LPS at 1-1000 ng/ml for different periods of time. The greater LTB4 stimulation was found at LPS 100 ng/ml for 18 h incubation time. Preincubation of monocytes with cytochalasin B (CB) (5 micrograms/ml) for 15 min augmented the release of LTB4 when LPS was used. A dose-dependent inhibition was found when human monocytes were pretreated for 10 min with hrIL-1Ra at different concentrations (0.25-250 ng/ml) and then treated with LPS 100 ng/ml for 18 h. Maximum inhibition was observed at the highest concentration of hrIL-1Ra (250 ng/ml). Macrophages treated with a non-selective 5-lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA), used at 10 microM, added 15 min before LPS 100 ng/ml, produce a dose-dependent inhibition of LTB4. Cells pretreated with arachidonic acid, at various concentrations (10(-9)-10(-5) M) for 10 min and then treated with LPS 100 ng/ml for 18 h, were also inhibited in a dose-dependent manner by hrIL-1Ra in their production of LTB4. The inhibition of LTB4 release by hrIL-1Ra, in LPS-stimulated human monocytes, may suggest an important modulatory role for this new cytokine (monokine) in inflammation and immunity and may hold future therapeutic implications for diseases involving LTB4 as a mediator.
在活化的人单核细胞培养物中研究了人重组白细胞介素-1受体拮抗剂（hrIL-1Ra）对白三烯B4（LTB4）释放的影响。为刺激LTB4生成，使用脂多糖（LPS）作为激动剂。采用高灵敏度放射免疫分析法进行检测。用1-1000 ng/ml的LPS以不同时间处理细胞，采用标量浓度。在100 ng/ml LPS孵育18小时时发现对LTB4的刺激作用更强。当使用LPS时，用细胞松弛素B（CB）（5微克/毫升）预孵育单核细胞15分钟可增强LTB4的释放。当用人单核细胞在不同浓度（0.25-250 ng/ml）下用hrIL-1Ra预处理10分钟，然后用100 ng/ml LPS处理18小时时，发现呈剂量依赖性抑制。在hrIL-1Ra最高浓度（250 ng/ml）时观察到最大抑制作用。用10 microM的非选择性5-脂氧合酶抑制剂去甲二氢愈创木酸（NDGA）在100 ng/ml LPS加入前15分钟处理巨噬细胞，可产生对LTB4的剂量依赖性抑制。用不同浓度（10⁻⁹-10⁻⁵ M）的花生四烯酸预处理细胞10分钟，然后用100 ng/ml LPS处理18小时，hrIL-1Ra对其LTB4生成也呈剂量依赖性抑制。hrIL-1Ra对LPS刺激的人单核细胞中LTB4释放的抑制作用，可能提示这种新的细胞因子（单核因子）在炎症和免疫中具有重要的调节作用，并且可能对涉及LTB4作为介质的疾病具有未来的治疗意义。
