Effect on leukemia cell numbers of in vivo administration of immunotherapeutic agents is age-dependent.
On the basis of our previous findings that erythroleukemia-bearing mice of different ages responded positively to immunotherapy [indomethacin +/- recombinant interleukin (rIL-2)] in vivo [stimulated natural killer (NK) cells and increased life span], we aimed, in the present study, to determine if changes in these parameters could be correlated to change in erythroleukemia cell numbers. Infant (< 3 weeks old), young adult (5-8 weeks) and aged (> 10 months) DBA/2 mice were injected with erythroleukemia cells. Some mice remained untreated for the 10-day duration of the tumor-bearing period, while others were treated with either indomethacin alone for the 10 days from tumor inoculation, rIL-2 alone for the last 4 days of the 10-day tumor-bearing period, or with both indomethacin and rIL-2 as above. In all cases, both treated and untreated mice were killed at 10 days after tumor inoculation. Cytospot preparations from single cell suspensions of spleen and bone marrow, in all cases, were stained with MacNeal's tetrachrome hematologic stain and the relative and absolute number of erythroleukemia cells in these organs were determined using light microscopy. The results show that indomethacin- and/or rIL-2 treated leukemic infant and young adult mice have significantly lower numbers of erythroleukemia cells in both the spleen and bone marrow relative to untreated, leukemic mice of corresponding age. Leukemic aged mice, however, show no change in erythroleukemia cell numbers in either organ, regardless of treatment, paralleling our observations of a lack of immunotherapeutic value of these agents on NK cell production/function in aged mice.
Dussault
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Department of Anatomy and Cell Biology, McGill University, Montreal, Que., Canada.
Miller
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D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000375:Aging / Q000502:physiology*; D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D002452:Cell Count / Q000187:drug effects; D005622:Friend murine leukemia virus; D007167:Immunotherapy; D007213:Indomethacin / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000502:physiology; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology* / Q000628:therapy*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000473:pathology; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D007376:Interleukin-2; D011994:Recombinant Proteins; D007213:Indomethacin