Population dynamics of natural killer cells in the spleen and bone marrow of normal and leukemic mice during in vivo exposure to interleukin-2.

By quantitative and functional methods, changes were assessed in NK(ASGM-1+) cell numbers and NK cell-mediated lytic function of the spleen and bone marrow of mice bearing a tumor of hemopoietic origin (FLV-induced erythroleukemia) for 9 days +/- simultaneous administration of indomethacin (10 micrograms/ml drinking water) +/- rIL-2 (3x/day, 12 x 10(3) Units/injection) during the last 4 days of tumor-bearing. Recombinant IL-2 alone during the last 4 days of tumor-bearing increased both the NK(ASGM-1+) cell numbers (p less than 0.001) and the functional activity (24-fold) of the spleen. In the bone marrow, however, no change in the numbers of NK(ASGM-1+) cells was observed relative to untreated tumor-bearing mice, but the NK cell-mediated lytic activity of that organ was augmented 30-fold. The continuous presence of indomethacin from the onset of tumor-bearing prior to rIL-2 treatment during the last 4 days of tumor-bearing, further boosted both the already high, rIL-2 driven numbers of NK(ASGM-1+) cells in the spleen (p less than 0.01), as well as splenic NK cell lytic function (2-fold). In the bone marrow, continuous presence of indomethacin prior to and during the terminal 4 days of co-administration with rIL-2 increased 3-fold the numbers of NK(ASGM-1+) cells relative to that of the bone marrow of tumor-bearing mice given rIL-2 alone, and resulted in lytic activity of that organ which was 140% of that of the rIL-2 treated, tumor-bearing mice. The results indicate that under the combined influence of indomethacin and rIL-2, the production of NK(ASGM-1+) cells was augmented in the bone marrow of tumor-bearing mice, export of immature NK(ASGM-1+) cells from the bone marrow was increased, and import of immature NK(ASGM-1+) cells by the spleen was increased. The increased NK(ASGM-1+) cell numbers in each organ was reflected in increased lytic function.