Potentiation of the therapeutic index of interleukin-2 immunotherapy by combination with taurine in a syngeneic murine tumour model.
BACKGROUND
Administration of interleukin-2 (IL-2) is limited by the induction of the vascular leak syndrome (VLS).


OBJECTIVE
To examine the effect of taurine on the toxicity and antitumour activity of IL-2 in a B16 melanoma pulmonary metastases model.


METHODS
B16 melanoma cells were injected into female C57BL/6 mice. Macroscopic melanoma pulmonary foci were established by day 10 in untreated mice. Treated mice were randomised into treatment by rIL-2 alone, rIL-2 plus taurine or taurine alone. Control animals received saline. Mice were sacrificed on day 18. Lung metastases were counted in a blinded fashion with the aid of a dissecting microscope. Wet to dry lung weight was measured following lung removal. In another experiment animals were treated as above (n = 15 per group) and survival following treatment monitored.


RESULTS
Treatment with IL-2 and taurine significantly reduced lung nodules compared with IL-2 alone. Host survival was significantly enhanced. The wet to dry (w/d) ratios of lung weights in the group receiving IL-2/taurine were significantly less than IL-2 alone. Bronchoalveolar lavage protein fluid was reduced indicating reduced pulmonary injury.


CONCLUSIONS
These findings indicate that the combination of taurine with IL-2 augments the efficacy of this immunotherapy while reducing its associated dose-limiting toxicity.
Finnegan
N
N
Department of Surgery, Royal College of Surgeons, Education and Research Centre, Beaumont Hospital, Dublin, Ireland.
Toomey
D
D
Condron
C
C
Redmond
H P
HP
Da Costa
M
M
Bouchier-Hayes
D J
DJ
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D007376:Interleukin-2 / Q000627:therapeutic use*; D008545:Melanoma / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D013654:Taurine / Q000494:pharmacology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D007376:Interleukin-2; D013654:Taurine