Hematopoietic growth-promoting effects of natural killer cells in mice in response to in vivo administration of human interleukin-2.
BACKGROUND
Interleukin-2 (IL-2) is currently being evaluated as an anti-neoplastic agent because of its stimulatory effects on the immune system. However, little is known about the effects of systemic IL-2 administration on hematopoietic parameters.


OBJECTIVE
Recombinant human IL-2 (rHuIL-2) was administered to mice to evaluate its in vivo hematopoietic effects. The mechanism underlying the effects of rHuIL-2 administration was also determined.


METHODS
Mice were given 5 x 10(4) IU of rHuIL-2 for 5 days, and their hematopoietic progenitor cell status was determined as measured by growth in soft agar. Antiserum to natural killer (NK) cell-specific markers was used to ascertain if NK cells were responsible for the hematopoietic effects of rHuIL-2. NK cells were purified and cultured in vitro with rHuIL-2 and then adoptively transferred into syngeneic mice to determine the effects on hematopoiesis.


RESULTS
Treatment of mice with rHuIL-2 resulted in a significant increase in bone marrow and splenic hematopoietic progenitor cell content. Mice with severe combined immune deficiency (SCID), which lack T cells and B cells yet have NK cells, also responded to the myelostimulatory effects of rHuIL-2. However, removal of NK cells from the SCID mice with antiserum to NK cell-specific markers abrogated the myelostimulatory properties of rHuIL-2. Adoptive transfer of NK cells that were propagated in vitro with rHuIL-2 into mice also resulted in an increase in splenic hematopoietic progenitor cells.


CONCLUSIONS
rHuIL-2 exerts significant myelostimulatory effects after in vivo administration, and NK cells are responsible for at least some of these effects.


CONCLUSIONS
These results suggest that NK cells and rHuIL-2 may be of use clinically to promote hematopoiesis after bone marrow transplantation or in the face of other myelotoxic therapy in the treatment of cancer.
Murphy
W J
WJ
Biological Response Modifers Program, National Cancer Institute-Frederick Cancer Research and Development Center, Md 21702-1201.
Longo
D L
DL
D000818:Animals; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000502:physiology; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D011994:Recombinant Proteins / Q000494:pharmacology
D007376:Interleukin-2; D011994:Recombinant Proteins