EFFECT OF CYTOKINES IN HOST DEFENSE AND INFLAMMATION

几年来，LHD一直在描述炎症性 与前臂上隆起的浅表皮肤病变相关的反应 正常志愿者和患有各种疾病的患者， 炎症 LHD最近确定，人类渗出液 来自正常受试者的嗜中性粒细胞具有非常高水平的细胞相关的 IL-8（6900 pg/106 PMN），并在培养过程中自发释放IL-8。 在 相反，新鲜分离的外周血中性粒细胞含有非常低的水平， IL-8（38 pg/106 PMN）。 在37 ℃下孵育外周血PMN 用毒胡萝卜素，一种内质网抑制剂 Ca 2 +-ATP酶引起[Ca 2 +]i持续升高（归因于 细胞外钙内流），并与表达增加有关 IL-8 mRNA的表达和IL-8的产生和释放增加， 外周血中性粒细胞 细胞相关的IL-8水平是 与在渗出性中性粒细胞中观察到的那些相当。 此外，IL-8 毒胡萝卜素的产生被治疗浓度的 环孢菌素A 这些数据表明，通过迁移产生IL-8 中性粒细胞是一种自分泌机制， 炎性病灶的中性粒细胞增多。此外，环孢菌素A 由于其独特的性质， 对IL-8合成的影响。 在相关的研究中，我们已经表明，可溶性纤维蛋白原协同 趋化肽fmet-leu-phe（5 nM），以诱导IL-8产生。 较高的fmet-leu-phe激活剂量（100 nM）对 诱导IL-8产生。 这些关于纤维蛋白原的研究 研究粘附于细胞表面的中性粒细胞中IL-8的诱导作用。 细胞外基质蛋白以及中性粒细胞 体外趋化性。初步证据表明， 中性粒细胞对纤维蛋白原包被的板的作用引起IL-8的诱导 生产

For several years the LHD has been characterizing the inflammatory response associated with superficial skin lesions raised on the forearms of both normal volunteers and patients with various disorders of inflammation. The LHD recently determined that human exudative neutrophils from normal subjects have very high levels of cell associated IL-8 (6900pg/106 PMNs) and spontaneouly release Il-8 during culture. In contrast, freshly isolated peripheral blood PMNs contain very low levels of IL-8 (38 pg/106 PMNs). Incubation of peripheral blood PMNs at 37 degrees C with thapsigargin, an inhibitor of endoplasmic reticulum Ca2+-ATPase, causes a sustained elevation in [Ca2+]i (attributable to extracellular calcium influx) and is associated with increased expression of IL-8 mRNA and increased production and release of IL-8 from isolated peripheral blood neutrophils. Levels of cell-associated IL-8 are comparable to those observed in exudative neutrophils. In addition, IL-8 production by thapsigargin is inhibited by therapeutic concentrations of cyclosporin A. These data suggest that production of IL-8 by migrating neutrophils represents an autocrine mechanism for recruitment of additional neutrophils to inflammatory foci. Furthermore, cyclosporin A may may have important uses as an antiinflammatory agent by virtue of its effect on IL-8 synthesis. In related studies, we have shown that soluble fibrinogen synergizes with the chemotactic peptide fmet-leu-phe (5nM), to induce IL-8 production. A higher, activating dose of fmet-leu-phe (100nM) is not effective in inducing IL-8 production. These studies with fibrinogen have prompted investigation of the induction of IL-8 in neutrophils adherent to extracellular matrix proteins as well as neutrophils undergoing chemotaxis in vitro. Preliminary evidence suggests that adherence of neutrophils to fibrinogen-coated plates causes induction of IL-8 production.