Stimulation of prostaglandin E2 and thromboxane B2 production by human monocytes in response to interleukin-2.
Interleukin 2 (IL-2) is a potent lymphokine involved in the regulation of immune responses and is classically regarded as a stimulus for the activation and growth of T-cells. Recent reports have demonstrated the IL-2 dependent activation of human peripheral blood lymphocytes into lymphokine activated killer cells capable of lysing tumor cells both in vitro and in vivo. In this study we report data which clearly show IL-2 may also act to down-regulate the immune response by inducing the synthesis of arachidonic acid metabolites with known immunosuppressive actions. Stimulation of peripheral human blood monocytes with IL-2 caused an increased production of prostaglandin E2 (PGE2) and thromboxane (TXB2) in a dose-dependent manner. Kinetic analysis showed no increase above controls after 6 hours and maximal levels by 10 hours; elevated levels were maintained after 45 hours of incubation. After 20 hours of stimulation with 2000 U/ml IL-2, the level of PGE2 and TXB2 were greater than three-fold above controls, 0.7 and 19 ng/10(6) cells, respectively. The stimulation was relatively specific in that neither prostacyclin nor leukotrienes were produced in response to IL-2. These data demonstrate that IL-2 acts on human monocytes to induce the secretion of PGE2 and TXB2.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D015232:Dinoprostone; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011458:Prostaglandins E / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D013929:Thromboxane B2 / Q000096:biosynthesis*
D007376:Interleukin-2; D008070:Lipopolysaccharides; D011458:Prostaglandins E; D011994:Recombinant Proteins; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D015232:Dinoprostone; D007213:Indomethacin