Effect of immunosuppressive agents FK 506 and cyclosporin and steroids on the expression of IL-6 and its receptor by stimulated lymphocytes and monocytes.
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 FK 506 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 ng/ml FK 506 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-stimulated adherent MO with different concentrations of CyA and FK 506 induced a restoration of IL-6R expression. FK 506 was 100 time more effective in restoring IL-6R than CyA. This restoration of IL-6R was incomplete. FK 506, 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.
Moutabarrik
A
A
Department of Nephrology, Faculté de Medecine de Casablanca, Morocco.
Nakanishi
I
I
Takahara
S
S
Hachim
K
K
Bengahnem
M G
MG
Ramadani
B
B
Ishibashi
M
M
Zaid
D
D
D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D015850:Interleukin-6 / Q000097:blood*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D010835:Phytohemagglutinins; D019947:Receptors, Interleukin-6 / Q000097:blood*; D016559:Tacrolimus / Q000494:pharmacology*
D007166:Immunosuppressive Agents; D015850:Interleukin-6; D010835:Phytohemagglutinins; D019947:Receptors, Interleukin-6; D003907:Dexamethasone; D016572:Cyclosporine; D016559:Tacrolimus