Effects of macrophage colony-stimulating factor and interleukin-2 administration on NK1.1(+) cells in mice

We studied the effects of M-CSF and IL-2 on NK1.1(+) cell activity in vivo and in vitro. Administration of M-CSF increased the number of splenic NK1.1 (+) cells (vs. saline: P < 0.01). Moreover, the combination of M-CSF and IL -2 (M-CSF+IL-2) produced a synergistic expansion of the number of NK1.1+ ce lls compared with each single treatment (vs. saline: P < 0.001). The NK1.1( +) cells were isolated from the spleen of each treated mouse (four treatmen t groups: saline, IL-2 alone, M-CSF alone, M-CSF + IL-2) and their function s (IL-2-induced proliferation, IFN-gamma production and cytostatic activity ) were evaluated in vitro. The NK1.1(+) cells from M-CSF alone and M-CSF+IL -2 treated mice showed greater responsiveness in terms of IL-2-induced prol iferation, production of IFN-gamma and cytostatic activity than the cells f rom saline and IL-2 alone treated mice. The NK activity in vivo was enhance d by the administration of M-CSF and IL-2, as assessed by the 'Lung clearan ce assay' (clearance of Yac-l cells in lung). And the M-CSF + IL-2 treatmen t induced the highest NK activity of the four treatments. To show a practic al effect of upregulation of NK activity in vivo by M-CSF and IL-2 administ ration, the effect of the four treatments on an experimental tumor metastas is model was examined. The IL-2 alone, M-CSF alone and M-CSF +IL-2 treatmen t reduced the metastasis of B16 melanoma. And the M-CSF + IL-2 treatment pr oved of greater benefit to the antimetastatic activity than each single tre atment. Our results demonstrated that the administration of M-CSF increases the number of NK1.1(+) cells, which have good responsiveness to IL-2. Furt hermore, the combination treatment of M-CSF and IL-2 in vivo augments the i ncrease of NK1.1(+) cells. And these effects can contribute to the antimeta static activity in vivo. (C) 2000 International Society for Immunopharmacol ogy. Published by Elsevier Science Ltd. All rights reserved.