Human lymphoid target cells for the cytokine-inducing seleno-organic compounds

Several seleno-organic compounds including ebselen are known as antiinflammatory and antioxidant agents. They also have glutathione peroxidase-like activity and are inhibitors of leukotrienes and prostaglandins. We have recently discovered that these drugs are inducers of cytokines, mainly interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) and mitogenic interleukins in human peripheral blood leukocytes (PBL) but not in the mouse or rat lymphoid cells. We described a production of IFN-gamma and TNF-alpha by various subsets of PBL stimulated with 2-phenyl-1,2-benzisoselenazol-3(2H)-one (ebselen) or bis [2-(N-phenyl-carbamoyl)]phenyl diselenide. IFN-gamma was produced mainly by E-rosette positive lymphocytes. However, the presence of monocytes was required for the optimal production of IFN-gamma. Also soluble mediators released by monocytes enhanced IFN-gamma synthesis. On the other hand, TNF-alpha was produced mainly by the adherent monocytes. Its synthesis was enhanced by the addition of T or B lymphocytes or conditioned medium from the culture of the stimulated lymphocytes. The relative concentrations of the subsets of lymphocytes or monocytes was important for the maximum production of both IFN-gamma and TNF-alpha. High concentration of lymphocytes inhibited the cytokine production.