Ostensen M E, Thiele D L, Lipsky P E
Harold C. Simmons Arthritis Research Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-8887.
J Biol Response Mod. 1989 Feb;8(1):53-61.
The current studies examined the potential for additive or synergistic augmentation of human natural killer (NK) function by combined stimulation with tumor necrosis factor alpha (TNF-alpha) or interleukin-1 (IL-1) and interferon-alpha (IFN-alpha) or IL-2. The modest augmentative effect of preincubation with either IL-1 or TNF-alpha alone was most consistently shown when killing of an NK-resistant target was examined. Preincubation with the combination of IL-1 and TNF-alpha caused no additive effect on NK function. Following preincubation with IL-1 and IL-2 or TNF-alpha and IL-2, marked enhancement of NK activity was noted, particularly when lysis of the NK-resistant target Cur was assessed. Killing of K562 targets was more markedly augmented by costimulation with TNF-alpha and IL-2 than with IL-2 alone or the combination of IL-1 and IL-2. Finally, IFN-alpha in combination with either TNF-alpha or IL-1 markedly enhanced Cur lysis, whereas interferon-gamma failed to augment IL-1- or TNF-alpha-enhanced tumor lysis. These findings demonstrate the separate and cooperative effects on human NK function of TNF-alpha or IL-1 in combination with IL-2 or IFN-alpha and suggest that the appropriate combinations of such agents may serve as the basis for in vivo multiagent immunotherapeutic regimens.
目前的研究检测了通过肿瘤坏死因子α（TNF-α）或白细胞介素-1（IL-1）与干扰素-α（IFN-α）或IL-2联合刺激来增强人类自然杀伤（NK）功能的可能性，以实现相加或协同增强作用。单独用IL-1或TNF-α预孵育时，适度的增强作用在检测对NK抗性靶标的杀伤时最为一致地显示出来。用IL-1和TNF-α联合预孵育对NK功能没有相加作用。在用IL-1和IL-2或TNF-α和IL-2预孵育后，观察到NK活性显著增强，特别是在评估对NK抗性靶标Cur的裂解时。与单独使用IL-2或IL-1和IL-2联合相比，TNF-α和IL-2共刺激对K562靶标的杀伤增强更为明显。最后，IFN-α与TNF-α或IL-1联合可显著增强Cur裂解，而干扰素-γ未能增强IL-1或TNF-α增强的肿瘤裂解。这些发现证明了TNF-α或IL-1与IL-2或IFN-α联合对人类NK功能的单独和协同作用，并表明这些药物的适当组合可能作为体内多药免疫治疗方案的基础。
