Importance in timing of cyclophosphamide on the enhancement of interleukin-2-induced cytolysis.
We investigated the in vivo effects of cyclophosphamide (CY) on interleukin-2(IL-2)-induced cytolytic function and spleen cell immunophenotype. Pretreatment of A/J mice with CY (25 mg/kg or 75 mg/kg) i.p. on days -10 and -15 followed by IL-2 (50,000 U i.p. on days 0 to +3) resulted in increased lysis of YAC-1 target cells compared to the group receiving IL-2 without previous CY therapy. In contrast, when CY was given on day -5, the cytotoxicity against YAC-1 was not enhanced. Phenotypic analysis of splenocytes obtained from mice treated with CY on day -10 or -15 revealed a relative decrease in L3T4- and Lyt2-positive T cells. In vivo depletion of natural killer (NK) cells by anti-asialoGM1, prior to IL-2 therapy, abrogated the enhancing effect of CY on cytolysis while in vivo elimination of T cells by anti-L3T4 and anti-Lyt2 monoclonal antibodies did not, indicating that in the absence of T cell antigenic challenge, the increased cytolytic function after CY administration is probably mediated through NK cells. These findings provide evidence that CY may be used more effectively in IL-2-based immunotherapy protocols, if consideration is given to timing of CY and IL-2 administration.
Katsanis
E
E
Department of Pediatrics, University of Minnesota, Minneapolis 55455.
Bausero
M A
MA
Ochoa
A C
AC
Loeffler
C M
CM
Blazar
B R
BR
Leonard
A S
AS
Anderson
P M
PM
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage*; D005260:Female; D007376:Interleukin-2 / Q000008:administration & dosage*; D007694:Killer Cells, Natural / Q000502:physiology; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D010641:Phenotype; D013154:Spleen / Q000276:immunology; D013997:Time Factors
D007376:Interleukin-2; D003520:Cyclophosphamide