Interleukin 18 induces a synergistic enhancement of interferon gamma production in mixed murine spleen cell-tumor cell cultures: role of endogenous interleukin 12.
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.
Micallef
M J
MJ
Fujisaki Institute, Hayashibara Biochemical Laboratories, Okayama, Japan.
Tanimoto
T
T
Kohno
K
K
Ikegami
H
H
Kurimoto
M
M
D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000494:pharmacology; D018664:Interleukin-12 / Q000502:physiology*; D020382:Interleukin-18 / Q000494:pharmacology / Q000502:physiology*; D007694:Killer Cells, Natural / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000378:metabolism*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D020382:Interleukin-18; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma