Th2/Th1 switch induced by a single low dose of cyclophosphamide in a rat metastatic lymphoma model

Cancer Immunol Immunother. 2002 Jan;50(11):588-96. doi: 10.1007/s00262-001-0237-3. Epub 2001 Nov 16.


Cyclophosphamide (Cy) is an alkylating agent widely used in cancer chemotherapy. It has a bimodal effect on the immune system, depending on the dose and schedule of administration. We have previously demonstrated that a single low dose of Cy has an antimetastatic effect, achieved through immunomodulation, in lymphoma bearing rats. Such a treatment reduced the splenic production of IL-10, TGF-beta, and NO, restoring the lymphoproliferative capacity. A shift from immunosuppression to immunopotentiation induced by low-dose Cy treatment was mainly mediated by a decrease in IL-10 production. The present study focused on the analysis of the modulation of type-1 cytokine levels by treatment with a single low dose of Cy and the effect these cytokines (IL-2 and IFN-gamma) and IL-10 have on primary tumor and metastatic cell growth. Our results suggest that a single low dose of Cy induces a Th2/Th1 shift in the cytokine profile of lymphoma-bearing rats, which may be responsible for its antimetastatic effect. A direct action of IL-10 as a growth factor and IFN-gamma as a cytotoxic factor on metastatic cells is also shown.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / therapeutic use
  • Animals
  • Antineoplastic Agents, Alkylating / administration & dosage*
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Cyclophosphamide / administration & dosage*
  • Cyclophosphamide / therapeutic use
  • Female
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / immunology
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / immunology
  • Lymphatic Metastasis
  • Lymphoma / drug therapy*
  • Lymphoma / immunology*
  • Lymphoma / pathology
  • Male
  • Rats
  • Th1 Cells / immunology*
  • Th2 Cells / immunology*


  • Adjuvants, Immunologic
  • Antineoplastic Agents, Alkylating
  • Interleukin-2
  • Interleukin-10
  • Interferon-gamma
  • Cyclophosphamide