Chirivi R G, Garofalo A, Padura I M, Mantovani A, Giavazzi R
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Cancer Res. 1993 Oct 15;53(20):5051-4.
This study examined the ability of the recombinant human interleukin 1 receptor antagonist (IL-1ra) to block interleukin 1 (IL-1)-mediated experimental metastases from the A375M human melanoma. In vivo, IL-1ra administrated at concentrations > or = 200 times IL-1 significantly inhibited the increase in lung colonies induced by IL-1 in nude mice. The response to IL-1 was significantly inhibited when IL-1ra was administered simultaneously with or 1 to 3 h before IL-1. In vitro, the incubation of IL-1-activated endothelial cells with IL-1ra prevented the increase in adhesion of A375M melanoma cells. At the same experimental conditions, IL-1ra inhibited the augmented expression of the intracellular and vascular cell adhesion molecules 1 and E-selectin induced by IL-1 on endothelial cells. Lipopolysaccharide, an IL-1 inducer, increased the number of lung colonies in nude mice. IL-1ra injected with or 1 h after lipopolysaccharide inhibited this augmentation, suggesting a role for host-produced IL-1 in metastasis formation.
本研究检测了重组人白细胞介素1受体拮抗剂（IL-1ra）阻断白细胞介素1（IL-1）介导的A375M人黑色素瘤实验性转移的能力。在体内，以大于或等于IL-1浓度200倍的浓度给予IL-1ra可显著抑制裸鼠中由IL-1诱导的肺集落增加。当与IL-1同时或在IL-1之前1至3小时给予IL-1ra时，对IL-1的反应受到显著抑制。在体外，用IL-1ra孵育IL-1激活的内皮细胞可阻止A375M黑色素瘤细胞黏附增加。在相同实验条件下，IL-1ra抑制了IL-1诱导的内皮细胞上细胞内黏附分子1、血管细胞黏附分子1和E-选择素的表达增加。脂多糖作为一种IL-1诱导剂，增加了裸鼠肺集落的数量。与脂多糖同时或在脂多糖注射后1小时注射IL-1ra可抑制这种增加，提示宿主产生的IL-1在转移形成中起作用。
