Early expression of interleukin-12, p40 subunit and IFN-gamma inhibits regression of AK-5 tumor.
Differential immune response of syngeneic animals to a rat histiocytoma AK-5 based on the route of transplantation was investigated. Spontaneous regression of subcutaneous tumor was observed in 55-60% of animals. On the other hand, when the tumor cells were injected intraperitoneally, none of the animals survived. Earlier studies from this laboratory indicated upregulation of Th-1-type cytokines, leading to early tumor regression when the tumor was transplanted subcutaneously. Hence we evaluated and compared the circulatory-cytokine profiles in both s.c. and i.p. tumor-injected animals. Our results show an early increase in the p40 subunit of IL-12, prolific increase in IFN-gamma and lower levels of IL-2 in i.p. tumor-injected animals. However, there were no significant differences in the levels of transcripts for these cytokines in either of the groups. Significantly, a lower level of cytotoxicity was observed with splenocytes from i.p. tumor-transplanted animals. Moreover, the cytotoxicity of IL-12-activated but not IL-2-activated NK cells was inhibited by sera (rich in IL-12, p40 subunit) from i.p. tumor-transplanted animals, suggesting the participation of p40 subunit in the regulation of tumor regression. Thus the present study suggests a possible translational regulation of Th-1-type cytokines in AK-5 tumor-host interaction.
Nandakumar
K S
KS
Centre for Cellular and Molecular Biology, Hyderabad, India.
Kumari
A L
AL
Khar
A
A
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology; D016207:Cytokines / Q000097:blood / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D015972:Gene Expression Regulation, Neoplastic; D018219:Histiocytoma, Benign Fibrous / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D007106:Immune Sera / Q000494:pharmacology; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics* / Q000494:pharmacology; D018664:Interleukin-12 / Q000097:blood / Q000235:genetics* / Q000494:pharmacology; D007376:Interleukin-2 / Q000097:blood / Q000235:genetics; D009365:Neoplasm Regression, Spontaneous; D009368:Neoplasm Transplantation; D012313:RNA / Q000032:analysis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D015375:Receptors, Interleukin-2 / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology / Q000637:transplantation
D000276:Adjuvants, Immunologic; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D016207:Cytokines; D007106:Immune Sera; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D018664:Interleukin-12; D012313:RNA; D007371:Interferon-gamma