Ogata K, Tamura H, Yokose N, An E, Dan K, Hamaguchi H, Sakamaki H, Onozawa Y, Clark S C, Nomura T
Third Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
Br J Haematol. 1995 May;90(1):15-21. doi: 10.1111/j.1365-2141.1995.tb03375.x.
The effects of interleukin 12 (IL-12) on natural killer (NK) cell cytotoxicity and on the production of interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) were examined in 15 patients with myelodysplastic syndromes (MDS), which are well known to have immunologic defects, and in 11 normal subjects. The NK cell cytotoxicity of all of the normal subjects was augmented by incubation with IL-12 alone, and co-incubation with interleukin 2 (IL-2) further augmented it (type A response). The MDS patients showed varied responses to IL-12/IL-2. Seven patients showed the type A response, resulting in augmented NK cell cytotoxicity which was similar to that in the normal subjects. In five other patients the cytotoxicity was not increased by IL-12 alone, but the combination of IL-12 and IL-2 did augment the cytotoxicity (type B response). The augmented cytotoxicity in these type B patients was lower than that in the normal subjects. In the final three MDS patients the cytotoxicity was low and not affected by IL-12 and/or IL-2 (type C response). All patients with refractory anaemia with excess blasts (RAEB) and patients with RAEB in transformation showed a type B or C response. Conversely, six of eight refractory anaemia patients showed a type A response. In MDS patients there was a positive correlation between the percentage of CD3- CD56+ cells in pre-incubated cells and the cytotoxicity of cells incubated with IL-12/IL-2. The combination of IL-12 and IL-2 augmented IFN-gamma and TNF-alpha production by nonadherent mononuclear cells in a synergistic or cumulative manner, respectively, in most patients. These results suggest that IL-12, alone or with IL-2, may modulate these important immunologic functions in most MDS patients.
在15例已知存在免疫缺陷的骨髓增生异常综合征（MDS）患者和11名正常受试者中，研究了白细胞介素12（IL - 12）对自然杀伤（NK）细胞细胞毒性以及干扰素 - γ（IFN - γ）和肿瘤坏死因子 - α（TNF - α）产生的影响。所有正常受试者的NK细胞细胞毒性在单独与IL - 12孵育时增强，而与白细胞介素2（IL - 2）共同孵育则进一步增强（A型反应）。MDS患者对IL - 12/IL - 2表现出不同反应。7例患者表现为A型反应，导致NK细胞细胞毒性增强，与正常受试者相似。另外5例患者单独使用IL - 12时细胞毒性未增加，但IL - 12和IL - 2联合使用确实增强了细胞毒性（B型反应）。这些B型患者增强的细胞毒性低于正常受试者。最后3例MDS患者细胞毒性低，且不受IL - 12和/或IL - 2影响（C型反应）。所有伴有过多原始细胞的难治性贫血（RAEB）患者和转化中的RAEB患者均表现为B型或C型反应。相反，8例难治性贫血患者中有6例表现为A型反应。在MDS患者中，预孵育细胞中CD3 - CD56 +细胞的百分比与用IL - 12/IL - 2孵育的细胞的细胞毒性之间存在正相关。在大多数患者中，IL - 12和IL - 2的组合分别以协同或累积方式增强了非贴壁单核细胞的IFN - γ和TNF - α产生。这些结果表明，IL - 12单独或与IL - 2联合使用可能调节大多数MDS患者的这些重要免疫功能。
