Effects of macrophage-colony-stimulating factor on cyclophosphamide-injected mouse NK1.1(+) cell activity

We injected cyclophosphamide into mice and examined their natural killer (N K) activity both in vitro and in vivo. Cyclophosphamide injection temporari ly abrogated the lung clearance activity of Yac-1 lymphoma tells. which is considered to be an index of NK activity in vivo. However, administration o f recombinant human macrophage-colony-stimulating-factor (rhM-CSF) to cyclo phosphamide-injected mice restored the lung clearance activity. To clarify whether the administration of rhM-CSF activated NK cells, we purified NK1.1 (+) cells from mice treated with cyclophosphamide and/or rhM-CSF and examin ed their functions (cytotoxicity, proliferation, and interferon gamma produ ction) in vitro. Cyclophosphamide injection decreased the number. but did n ot suppress the functions of NK1.1(+) cells. The numbers of NK1.1(+) cells in cyclophosphamide-injected mice restored by rhM-CSF administration. And t he functions of NK1.1(+) cells from both saline-injected and cyclophosphami de-injected mice were accelerated by rhM-CSF administration. These results suggested that the temporary abrogation of NK activity in vivo caused by cy clophosphamide injection was due to a decrease in the number and not to sup pression of the functions of NK1.1(+) cells. The injection of cyclophospham ide into mice increased the number of tumor (B16 melanoma) nodules formed i n the lungs and liver. However, treatment with rhM-CSF recovered the anti-m etastatic activity in the lungs of cyclophosphamide-injected mice. These re sults show that administration of rhM-CSF restores NK activity suppressed b y cyclophosphamide injection in vivo.