Enhancement of human natural killer cell function by the combined effects of tumor necrosis factor alpha or interleukin-1 and interferon-alpha or interleukin-2.

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.