STUDY ON ANTI-TUMOUR EFFECTS OF INTERLEUKIN12 FOR SPONTANEOUSLY AROSE MURINE RENAL CELL CARCINOMA

BACKGROUND We studied on the anti-tumour effects of recently cloned cytokine interleukin-12 (IL-12) for murine renal cell carcinoma (RC-2) with special reference to the difference of its activity based upon the different method of administration. MATERIALS AND METHODS Ten days after RC-2 inoculation to subcutaneous of BALB/C mice, the recombinant murine IL-12 (rMu-IL-12 was administered (0.5 microgram/mouse, 1.0 microgram/mouse and 2.0 micrograms/mouse) 5 times per week for 3 weeks. Two administration methods were applied: intraperitoneal administration (i.p.) and subcutaneous administration near grown tumour (s.c.). We evaluated the efficacy of IL-12 for the RC-2 by means of the ratio of relative mean tumour weight (TRW/CRW), the degree of histological degeneration and the survival time of tumour-bearing mice. Furthermore, the serial body weight of mice excluding the tumour weight was monitored in order to evaluate the side effect of IL-12. RESULTS 1) The ratio of TRW/CRW: As to the experiment of IL-12 injected at 0.5 microgram/mouse, the anti-growth effect was more potent in the i.p. group than in the s.c. group. On the other hand, as to the higher dose groups including 1.0 microgram/mouse and 2.0 micrograms/ mouse groups, the s.c. groups showed more potent anti-tumour growth effects than the i.p. groups. 2) The histological effect: All examined groups showed the degree of grade II degeneration which meant the existence of viable tumour cells after the treatment had been finished. Furthermore, we found out the different pattern of degeneration between the two administration groups (i.p. and s.c.). Namely, there observed sporadicaly degeneration in the i.p. groups, and also observed uniform degeneration close to the injected area in the s.c. groups. 3) Survival time: All treated groups showed a significant prolongation of survival compared with the control, but no significant difference was observed between these two different injected groups. 4) Side effects: Through monitoring serial changes of body weight of treated mice, no significant decrease of body weight due to the administration of IL-12 was observed in all experiments. CONCLUSION The anti-tumour effects of IL-12 for murine renal cell carcinoma with special reference to the difference of anti-tumour effect based upon the different method of administration shows that more potent anti-tumor growth effects are observed in the i.p. group dosed at 0.5 microgram/mouse than in the s.c. group. On the other hand, as to the escalating doses, more potent anti-tumour effects are observed in the s.c. groups than in the i.p. groups. Through all treatment groups, no complete regression of the tumour is observed. Therefore, further precise study to clarify the immunological reaction between tumour and its host derived from the administration of IL-12 must be needed in order to establish more effective treatment with IL-12 in the future.