Thomsen M K, Larsen C G, Thomsen H K, Kirstein D, Skak-Nielsen T, Ahnfelt-Rønne I, Thestrup-Pedersen K
Department of Pharmacology, Leo Pharmaceutical Products, Ballerup, Denmark.
J Invest Dermatol. 1991 Feb;96(2):260-6. doi: 10.1111/1523-1747.ep12464458.
Interleukin-8 (IL-8), formerly known as NAP-1, is formed by a variety of cells upon stimulation with IL-1 or tumor necrosis factor (TNF). The biologic activity of the cytokine involves activation of almost every neutrophil function studied so far in different species. In the present study, we compared the effects of recombinant human IL-8 (rIL-8) and the lipid mediators, leukotriene B4 (LTB4) and platelet-activating factor (PAF), on neutrophil functions in dogs. All three chemotactic factors induced neutrophil aggregation and chemotaxis, with rIL-8 being far more potent than LTB4 and PAF. The migration induced by rIL-8 was significantly greater than that observed towards LTB4 and PAF. In the aggregation assay, rIL-8 was shown for the first time to be a potent stimulant. The aggregation response was more persistent than that obtained with LTB4 and PAF and the potency of rIL-8 was greater. An intradermal dose-response study showed that rIL-8 is an extremely potent inducer of selective neutrophil infiltration in canine skin. The infiltration was more pronounced than following injection of LTB4 or PAF. It was proposed that the superior effect of rIL-8 was caused by a synergistic effect between injected rIL-8 and LTB4, which was shown to be produced in biologically active amounts by canine neutrophils stimulated with rIL-8. From a therapeutic point of view, the simultaneous presence of rIL-8 and LTB4 in inflammatory skin diseases highlights the need to develop drugs that inhibit the production and/or effect of both mediators.
白细胞介素-8（IL-8），以前称为中性粒细胞激活蛋白-1（NAP-1），是多种细胞在受到白细胞介素-1（IL-1）或肿瘤坏死因子（TNF）刺激后形成的。这种细胞因子的生物学活性几乎涉及到目前在不同物种中所研究的每一种中性粒细胞功能的激活。在本研究中，我们比较了重组人IL-8（rIL-8）与脂质介质白三烯B4（LTB4）和血小板活化因子（PAF）对犬中性粒细胞功能的影响。所有这三种趋化因子均能诱导中性粒细胞聚集和趋化，其中rIL-8的作用远比LTB4和PAF强大。rIL-8诱导的迁移明显大于对LTB4和PAF观察到的迁移。在聚集试验中，rIL-8首次被证明是一种有效的刺激剂。其聚集反应比LTB4和PAF更持久，且rIL-8的效力更大。皮内剂量反应研究表明，rIL-8是犬皮肤中选择性中性粒细胞浸润的一种极其有效的诱导剂。这种浸润比注射LTB4或PAF后更明显。有人提出，rIL-8的优越作用是由注射的rIL-8与LTB4之间的协同作用引起的，研究表明，用rIL-8刺激的犬中性粒细胞能产生生物活性量的LTB4。从治疗角度来看，炎症性皮肤病中rIL-8和LTB4的同时存在突出了开发抑制这两种介质产生和/或作用的药物的必要性。
