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


CONCLUSIONS
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.
Chen
Yuh-Min
YM
Chest Department, Taipei Veterans General Hospital, National Yang-Ming University School of Medicine, and Institute of Cancer Research, National Health Research Institutes, Taipei, Taiwan, R.O.C. ymchen@vghtpe.gov.tw
Wang
Pi-Sheng
PS
Liu
Jacqueline Ming
JM
Hsieh
Yi-Lin
YL
Tsai
Chun-Ming
CM
Perng
Reury-Perng
RP
Whang-Peng
Jacqueline
J
D000367:Age Factors; D000818:Animals; D005260:Female; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D018664:Interleukin-12 / Q000008:administration & dosage; D007376:Interleukin-2 / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000556:secondary*; D008546:Melanoma, Experimental / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D007376:Interleukin-2; D042461:Vascular Endothelial Growth Factor A; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma