Effect of immunosuppressive agents FK506 and cyclosporin and steroids on the expression of IL‐6 and its receptor by stimulated lymphocytes and monocytes

Abstract The interaction of interleukin‐6 (IL‐6) with its receptor (IL‐ 6R) is not well understood. In the present study, we investigated the effect of different immunosuppressive agents on the expression of the couple IL‐6/ IL‐6R on cultured lymphocytes and monocytes. IL‐6 in culture supernatants from cultured monocytes were analyzed by ELISA. The expression of IL‐6R was studied by flow cytometry. Dexamethazone, cyclosporin (CyA), and FK506 at immunosuppressive concentrations induced a dose‐dependent inhibition of IL‐6 secretion from adherent monocytes (MO) stimulated with phytohemagglutinin (PHA). Dexamethazone was the most effective agent in inhibiting IL‐6 secretion, while the inhibitory effect observed with 1 ngyml FK506 was comparable with that obtained with 100 ng/ml CyA. Unstimulated MO strongly expressed IL‐6R (80% positive cells). Stimulation of MO with PHA resulted in a significant downregulation of IL‐6R expression. Treatment of PHA‐timulated adherent MO with different concentrations of CyA and FK S06 induced a restoration of IL‐6 R expression. FKS06 was 100 time more effective in restoring IL‐6R than CyA. This restoration of IL‐6R was incomplete. FK506, CyA, and steroids may exert their immunosuppressive effect by inhibiting IL‐6 secretion and partially restoring MO IL‐6R, which may be important in protecting the cell target against IL‐6 autocrine stimulation. Copyright © 1994, Wiley Blackwell. All rights reserved