Effect of age on pulmonary metastases and immunotherapy in young and middle-aged mice

J Chin Med Assoc. 2007 Mar;70(3):94-102. doi: 10.1016/S1726-4901(09)70338-7.

Abstract

Background: We used B16-F10 (B16) melanoma tumor cells and syngeneic C57BL/6 (B6) mice as a study model for pulmonary metastases, to better understand whether or not there exist differences in tumorigenicity and in the effectiveness of immunotherapy as a function of host age (1-, 3-, 12- and 24-month-old).

Methods: Intravenous injection of B16 melanoma cells were administered to B6 mice of different ages with/without interleukin (IL)-2 and IL-12 daily treatment. Tumor growth, splenocyte function, serum cytokines (IL-10, interferon-gamma, vascular endothelial growth factor) and survival were compared.

Results: The study showed that, without IL-2 and IL-12 treatment, middle-aged mice suffering from pulmonary metastases had fewer pulmonary metastases and better survival than younger mice suffering from pulmonary metastases. Three days' IL-2 plus IL-12 treatment could not prolong mice survival, but prolonged treatment significantly improved the survival of both the younger and older tumor-bearing mice, especially the older mice, despite the fact that the younger mice had a better serum cytokine and splenocyte cellular immune response to cytokine treatment.

Conclusion: The young B6 mice that suffered from B16 pulmonary metastases had a poorer prognosis than the middle-aged mice. Short-term IL-2 plus IL-12 treatment is ineffective in prolonging survival, and a longer duration of treatment is needed. This kind of immunotherapy was effective in both the young and middle-aged mice, but it was more effective in the middle-aged mice.

MeSH terms

  • Age Factors
  • Animals
  • Female
  • Interferon-gamma / blood
  • Interleukin-10 / blood
  • Interleukin-12 / administration & dosage
  • Interleukin-2 / administration & dosage
  • Lung Neoplasms / secondary*
  • Melanoma, Experimental / mortality
  • Melanoma, Experimental / secondary
  • Melanoma, Experimental / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Vascular Endothelial Growth Factor A / blood

Substances

  • Interleukin-2
  • Vascular Endothelial Growth Factor A
  • Interleukin-10
  • Interleukin-12
  • Interferon-gamma