Potentiation of the therapeutic index of interleukin-2 immunotherapy by combination with taurine in a syngeneic murine tumour model

Abstract

Background: Administration of interleukin-2 (IL-2) is limited by the induction of the vascular leak syndrome (VLS).

Aims: 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.

Result: 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.

Conclusion: These findings indicate that the combination of taurine with IL-2 augments the efficacy of this immunotherapy while reducing its associated dose-limiting toxicity.