Synergism between IFN-gamma and IL-1 alpha/beta in growth inhibition of an allografted tumor.
Soluble effector molecules involved in the rejection of allografted mouse Meth A (3-methylcholanthrene-induced ascites type tumor) cells were examined. A potent antiproliferative activity against the tumor cells was detected in the culture supernatant of leukocytes that had infiltrated into the peritoneal cavity of C57BL/6 mice on days 6-8 after transplantation, when the i.p. transplanted Meth A cells were undergoing rejection. Studies with neutralizing antibodies indicated that both IFN-gamma and IL-1 alpha/beta were required for the activity but that TNF-alpha was not. Actually, mouse rIFN-gamma and rIL-1 alpha/beta used, at the concentrations found in the culture supernatant determined by ELISA, were able to reconstitute the potent antiproliferative activity, although each cytokine alone had a weak growth inhibitory activity against Meth A cells. The half-maximal inhibition was observed with 0.02-0.03 U/ml of rIL-1 alpha/beta at 1-100 U/ml of rIFN-gamma. The synergistic growth inhibitory effect of these cytokines also was observed with four of 15 mouse transformed cell lines tested, indicating that the effect was not specific to Meth A cells. These findings suggest that IFN-gamma and IL-1 alpha/beta participate as soluble effector molecules in the rejection of some allografted tumor cells including Meth A cells.
Takikawa
O
O
Department of Cell Biology, Osaka Bioscience Institute, Japan.
Oku
T
T
Yasui
H
H
Yoshida
R
R
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D006131:Growth Inhibitors; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000008:administration & dosage*; D007375:Interleukin-1 / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D006131:Growth Inhibitors; D007375:Interleukin-1; D011994:Recombinant Proteins; D007371:Interferon-gamma