Coproduction of interleukin-2 and interferon-gamma in human mononuclear cells.
Interleukin-2 (IL-2) and immune interferon (IFN-gamma) production was studied in Ficoll-hypaque purified human mononuclear cells derived from plateletpheresis residues. As previously reported, costimulation by 5 ng/ml of 12-O-tetradecanoylphorbol-13-acetate (TPA) and 5 microgram/ml of phytohemagglutinin (PHA) caused a marked enhancement of IFN-gamma levels compared to the yields obtained with PHA alone. IL-2 levels were also increased 50-300 times by this induction protocol. Mezerein (MZN), a compound structurally related to TPA, was found to be similar to TPA in enhancing IFN-gamma and IL-2 levels. In addition to TPA and MZN, four other related phorbol esters caused a stimulation of IFN-gamma and IL-2, with the production of IL-2 paralleling the production of IFN-gamma. Kinetic experiments indicate that low levels of IL-2 first became detectable 6 h after induction, whereas IFN-gamma could be demonstrated only later. Furthermore, IL-2 production reached a plateau earlier than IFN-gamma production in the TPA/PHA treated cultures. Dialysis at pH 2 abrogated the IFN-gamma activity but not the IL-2 activity. A three-step purification procedure developed for IFN-gamma isolation effectively separated IFN-gamma from IL-2. Our results show that there is a close correlation between the magnitude of IL-2 and IFN-gamma production under the experimental conditions employed. Physical separation of the two lymphokines is important for future studies on the interactions between IFN-gamma and IL-2 in various cellular immune reactions.
D002478:Cells, Cultured; D004224:Diterpenes; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D013729:Terpenes; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism
D004224:Diterpenes; D007376:Interleukin-2; D010703:Phorbol Esters; D010835:Phytohemagglutinins; D013729:Terpenes; C011309:mezerein; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine