ADMINISTRATION OF RECOMBINANT IL-12 TO NORMAL MICE ENHANCES CYTOLYTIC LYMPHOCYTE ACTIVITY AND INDUCES PRODUCTION OF IFN-GAMMA IN-VIVO
ADMINISTRATION OF RECOMBINANT IL-12 TO NORMAL MICE ENHANCES CYTOLYTIC LYMPHOCYTE ACTIVITY AND INDUCES PRODUCTION OF IFN-GAMMA IN-VIVO
复制标题
DOI：
10.1093/intimm/6.1.157
复制
发表时间：
1994-01-01
影响因子：
4.4
通讯作者：
MURPHY, M
中科院分区：
文献类型：
--
作者：
GATELY, MK;WARRIER, RR;MURPHY, M
IL-12是一种异源二聚体细胞因子，已显示其增强自然杀伤（NK）和细胞毒性T淋巴细胞（CTL）应答，并在体外诱导IFN-γ产生。在这项研究中，我们已经检查了对正常小鼠施用纯化的鼠rIL-12的体内效果。每天腹腔注射rIL-12（1 ng至10 μ g/天），可引起治疗小鼠脾和肝中NK细胞溶解活性的剂量依赖性增强。IL-12处理小鼠肝脏的组织学检查显示局灶性单核细胞浸润，流式细胞术研究表明IL-12处理小鼠肝脏含有数量增加的NK细胞、CD 8（+）T细胞和单核细胞。与对照小鼠的肝和脾淋巴细胞不同，IL-12处理小鼠的肝和脾淋巴细胞在体外自发分泌IFN-γ，表明它们已被IL-12诱导在体内产生IFN-γ。与此一致，在IL-12处理的小鼠的血清中可以检测到IFN-γ。在通过足垫注射同种异体脾细胞免疫的小鼠中，每天腹腔注射rIL-12显示出增强引流淋巴结中的特异性CTL应答。因此，这些研究表明，IL-12可以增强NK和CTL活性，并在体内以及体外诱导IFN-γ的产生，并提出了IL-12可能在治疗某些肿瘤和感染性疾病中发挥治疗作用的可能机制。
IL-12 is a heterodimeric cytokine that has been shown to enhance natural killer (NK) and cytotoxic T lymphocyte (CTL) responses, and to induce IFN-gamma production in vitro. In this study, we have examined the effects in vivo of administering purified murine rlL-12 to normal mice. Daily injections of rIL-12 i.p. (1 ng to 10 mu g/day) caused dose-dependent enhancement of NK cell lytic activity in the spleens and livers of treated mice. Histologic examination of the livers of IL-12-treated mice revealed focal mononuclear cell infiltrates, and flow cytometry studies indicated that the livers of IL-12-treated mice contained increased numbers of NK cells, CD8(+) T cells, and monocytes. Liver and splenic lymphoid cells from Il-12-treated mice, unlike liver and splenic lymphoid cells from control mice, spontaneously secreted IFN-gamma in vitro, suggesting that they had been induced by IL-12 to produce IFN-gamma in vivo. Consistent with this, IFN-gamma could be detected in the serum of IL-12-treated mice. In mice which had been immunized by footpad injection of allogeneic splenocytes, daily administration of rIL-12 i.p. was shown to enhance the specific CTL response in the draining lymph nodes. Thus, these studies demonstrate that IL-12 can enhance NK and CTL activity and induce IFN-gamma production in vivo, as well as in vitro, and suggest possible mechanisms by which IL-12 may exert therapeutic effects in the treatment of some tumors and infectious diseases.