The addition of interleukin-2 to cyclophosphamide therapy can facilitate tumor growth of B16 melanoma.
The role of interleukin-2 (IL-2) on tumor growth of B16F10 melanoma cells was assessed in two sets of mice with different immune status: normal (immunocompetent) mice and immunodeficient mice. The two sets of animals were treated with cyclophosphamide (CY) or IL-2 alone or with a combined therapy of CY+IL-2. On days 6 and 10 after tumor cell injection, we evaluated the incidence of hepatic B16 melanoma metastases and the percentage of hepatic volume occupied by metastatic tissue. We observed that the CY alone (300 mg/kg, days 3 and 8 post-tumoral inoculation) significantly reduced tumor growth in all treated mice; however, CY proved more effective in normal recipients than in immunodeficient hosts. On the other hand, whereas administration of IL-2 alone (10(5) IU daily, from day 3 to day 7) in immunocompetent mice significantly reduced tumor growth on days 6 and 10, in immunodeficient mice, no significant differences were observed in tumor growth either on the 6th or on the 10th day, in comparison to control groups. Finally, when the combined CY+IL-2 therapy was administered, an antisynergistic effect between these therapeutic agents was achieved both in normal and in immunodeficient mice. Thus, the addition of low-dose IL-2 (25 x 10(3) IU daily, from day 4 to day 7) to high-dose CY (300 mg/kg, days 3 and 8) significantly increased tumor growth in both the early and later periods, compared to the effect of CY alone. It is concluded that exogenous IL-2 can facilitate tumor growth of B16 melanoma cells in vivo.
Palomares
T
T
Department of Surgery, Radiology and Physical Medicine, School of Medicine and Dentistry, University of the Basque Country, Leioa, Vizcaya, Spain.
Bilbao
P
P
Alonso-Varona
A
A
Barberá-Guillem
E
E
D000818:Animals; D003131:Combined Modality Therapy / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use*; D004347:Drug Interactions; D005260:Female; D007121:Immunocompetence; D016867:Immunocompromised Host; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D007267:Injections; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000556:secondary / Q000628:therapy; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000276:immunology / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000378:metabolism; D009368:Neoplasm Transplantation; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000378:metabolism; D013154:Spleen; D014916:Whole-Body Irradiation / Q000009:adverse effects
D007155:Immunologic Factors; D007376:Interleukin-2; D009363:Neoplasm Proteins; D015375:Receptors, Interleukin-2; D003520:Cyclophosphamide