In vitro effects of retinoids on mitogen-induced peripheral blood leucocyte responses

The aim of the present study was to investigate the influence of three different retinoids, isotretinoin, etretinate and acitretin, on the mitogenic response of peripheral blood mononuclear cells (PBMCs) to PHA and PMA in vitro. All three retinoids at high concentrations (10(-4)M) significantly inhibited the mitogenic response of PBMCs to these mitogens. At lower concentrations (10(-5) M and 10(-6) M) none of the three retinoids had any effect on PBMC proliferation in response to PHA. Interestingly, isotretinoin and etretinate significantly enhanced the PMA-induced stimulation of proliferation, whereas acitretin at 10(-5) M failed to influence the mitogenic response to PMA but enhanced it at 10(-6) M. The enhancing effects of retinoids on the proliferative response of PMA-stimulated PBMCs were reversed by rapamycin (10 ng/ml), an immunosuppressant known to inhibit the phorbol ester-induced protein kinase C pathway of lymphocyte activation. In conclusion, our study indicates that retinoids directly trigger the PMA-induced protein kinase C pathway of lymphocyte activation in a concentration-dependent manner. This observation could explain the findings of previous studies showing an in vivo immunopotentiating effect of retinoids on certain immune functions.