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.
Department of Radiation Medicine, University of Kentucky, Chandler Medical Center, Lexington 40536-0084.
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M
Taradi
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Urano
S K
SK
Taradi
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Y
Maruyama
D000818:Animals; D003131:Combined Modality Therapy; D003602:Cytotoxicity, Immunologic; D005354:Fibrosarcoma / Q000276:immunology / Q000532:radiotherapy / Q000628:therapy*; D006979:Hyperthermia, Induced; D016219:Immunotherapy, Adoptive; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000276:immunology*; D008212:Lymphocyte Depletion; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D010844:Picibanil / Q000008:administration & dosage*; D013601:T-Lymphocytes / Q000276:immunology
D010844:Picibanil