Nakagawa N, Nakagawa T, Acres B, Yasukawa K, Kieny M P
Transgene S.A., Strasbourg, France.
Eur Cytokine Netw. 1991 Jan-Feb;2(1):11-6.
We have constructed a recombinant vaccinia virus (VV) expressing the human interleukin-6 (IL-6) gene, VV(IL-6). After injection of VV(IL-6) i.v. into Balb/c mice, circulating IL-6 was detected during 3 days with the peak activity on day 4, indicating that VV injection is an effective method to deliver lymphokines in vivo. We have further examined the effects of IL-6 in vivo in immunodeficient mice. Nude mice were injected i.v. with VV(IL-6). Ten days after the injection, mice were sacrificed and spleen cells were obtained. Spleen cells from VV(IL-6) injected mice proliferated remarkably in response to IL-2, while spleen cells from mice injected with unrelated VV manifested no particular proliferation in response to lymphokines. When spleen cells were further cultured in vitro for 5 days in the presence of Concanavalin-A stimulated rat spleen cell supernatant (Con-A factor), CD4 or CD8 positive cells were detected in the VV (IL-6) injected group, while few positive cells were detected in the control groups. These results suggest that IL-6 stimulates nude mice spleen cells in vivo, to a stage where they are able to proliferate in response to IL-2, or to differentiate into CD4 or CD8 positive cells in presence of rat Con-A factor.
我们构建了一种表达人白细胞介素-6（IL-6）基因的重组痘苗病毒（VV），即VV（IL-6）。将VV（IL-6）静脉注射到Balb/c小鼠体内后，在3天内检测到循环中的IL-6，其活性在第4天达到峰值，这表明注射VV是在体内递送淋巴因子的有效方法。我们进一步研究了IL-6在免疫缺陷小鼠体内的作用。给裸鼠静脉注射VV（IL-6）。注射10天后，处死小鼠并获取脾细胞。注射VV（IL-6）的小鼠的脾细胞对IL-2有显著增殖反应，而注射无关VV的小鼠的脾细胞对淋巴因子无特殊增殖反应。当脾细胞在伴刀豆球蛋白A刺激的大鼠脾细胞上清液（伴刀豆球蛋白A因子）存在的情况下进一步体外培养5天时，在注射VV（IL-6）的组中检测到CD4或CD8阳性细胞，而在对照组中检测到的阳性细胞很少。这些结果表明，IL-6在体内刺激裸鼠脾细胞，使其达到能够对IL-2产生增殖反应的阶段，或者在大鼠伴刀豆球蛋白A因子存在的情况下分化为CD4或CD8阳性细胞。
