PMID- 10975285 OWN - NLM STAT- MEDLINE DCOM- 20010125 LR - 20100510 IS - 0361-090X (Print) IS - 0361-090X (Linking) VI - 24 IP - 3 DP - 2000 TI - Interleukin 18 induces a synergistic enhancement of interferon gamma production in mixed murine spleen cell-tumor cell cultures: role of endogenous interleukin 12. PG - 234-43 AB - Interleukin 18 (IL-18) reportedly synergizes with IL-12 and IL-10 for interferon gamma (IFN-gamma) synthesis and natural killer (NK) cell activity, respectively. Here we show that IL-18 alone induces low level IFN-gamma production by unstimulated Balb/c mouse spleen cells, but production is enhanced synergistically in cocultures of spleen cells and allogeneic living or fixed Yac-1 cells. Spleen cells could be primed with IL-18 prior to coculture with Yac-1 cells for IFN-gamma production, which also was observed in cocultures containing either syngeneic or xenogeneic tumor cells. IFN-gamma production in stimulated cocultures was abrogated almost completely by anti-IL-12 antibody and was unrelated to spleen cell lytic activity. IL-10 moderately inhibited IFN-gamma production induced by IL-18. Therefore, in spleen cell and tumor cell cocultures exposed to IL-18, high levels of IFN-gamma are produced by the spleen cells arising from a synergistic interaction between the exogenous IL-18 and endogenous IL-12; however, this activity is unrelated to the spleen cell lytic activity. FAU - Micallef, M J AU - Micallef MJ AD - Fujisaki Institute, Hayashibara Biochemical Laboratories, Okayama, Japan. FAU - Tanimoto, T AU - Tanimoto T FAU - Kohno, K AU - Kohno K FAU - Ikegami, H AU - Ikegami H FAU - Kurimoto, M AU - Kurimoto M LA - eng PT - Journal Article PL - England TA - Cancer Detect Prev JT - Cancer detection and prevention JID - 7704778 RN - 0 (Interleukin-18) RN - 130068-27-8 (Interleukin-10) RN - 187348-17-0 (Interleukin-12) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - Cells, Cultured MH - Coculture Techniques MH - Dose-Response Relationship, Drug MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Interferon-gamma/*biosynthesis MH - Interleukin-10/pharmacology MH - Interleukin-12/*physiology MH - Interleukin-18/pharmacology/*physiology MH - Killer Cells, Natural/metabolism MH - Mice MH - Mice, Inbred BALB C MH - Spleen/*metabolism MH - Time Factors MH - Tumor Cells, Cultured EDAT- 2000/09/07 11:00 MHDA- 2001/02/28 10:01 CRDT- 2000/09/07 11:00 PHST- 2000/09/07 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2000/09/07 11:00 [entrez] PST - ppublish SO - Cancer Detect Prev. 2000;24(3):234-43.