Augmentation of mouse natural killer cell activity by combined hyperthermia and streptococcal preparation, OK-432 (Picibanil) treatment.

It has previously been demonstrated that the local administration of OK-432 (Picibanil) enhances the response of a murine tumour and normal tissue to elevated temperatures. The experimental animals were C3Hf/Sed mice and the tumours were the fourth generation isotransplants of a spontaneous non-immunogenic fibrosarcoma, FSa-II. The thermal enhancement ratio was greater for the tumour than for normal tissue, resulting in a favourable differential effect between normal and malignant tissues. Further studies were conducted to disclose the mechanism of OK-432 induced thermal enhancement. Although OK-432 showed a slight direct cytotoxic activity against tumour cells in vitro, the in vivo antitumour effect of combined OK-432 and hyperthermia treatments was greater than the effect expected from in vitro cytotoxicity, indicating the involvement of the host-mediated mechanisms. Whole body irradiation (WBI), which suppressed the host's immune reaction, did not affect the thermal enhancement mediated by OK-432, suggesting that radiosensitive cells (sensitive to WBI) were not involved in this process. As expected, the i.v. injections of the anti-mouse T-cell serum did not have any effect on the thermal enhancement of OK-432. The administration of blockers of the reticuloendothelium system, i.e. silica or trypan blue, did not inhibit the OK-432 induced thermal enhancement. Moreover, local intratumoural injections of normal or OK-432 induced macrophages showed no effect on tumour growth. The thermal enhancement by OK-432 was eliminated following treatments with anti-(asialo GM1) globulin. Despite the fact that the cytotoxic effect of anti-(asialo GM1) globulin was not selective to natural killer (NK) cells, all the experimental results indicated that NK cells were probably attributable to thermal enhancement by OK-432 in vivo. The NK cell activity was stimulated when the OK-432 was locally administered with hyperthermia.