Potent and Selective Inhibition of in Vltro Lymphocyte Migration by Cyclosporine and Dexamethasone

We have studied the in vitro effects of cyclosporine A (CsA) and dexamethasone on lymphocyte migration, which is considered to play an important role in the pathogenesis of inflammatory and auto-immune disorders. Using a 48-well microchemotaxis assay, dose-related migratory responses of mixed peripheral blood lymphocytes (PBL) to recombinant interleukin (rIL)-1 alpha, rIL-2, leukotriene B4 (LTB4) and zymosan activated plasma (ZAP) were demonstrated. When preincubated with PBL under plasma free conditions and in the presence of undiluted autologous plasma, CsA in the dose range 4 x 10(-13)-1.6 x 10(-7) M caused concentration related inhibition of lymphocyte migration in response to fixed concentrations of rIL-1 alpha and rIL-2. CsA in the same dose range had no effect on the migration of PBL in response to ZAP and LTB4. Under plasma-free conditions dexamethasone (1 x 10(-11)-4 x 10(-6) M) caused concentration related inhibition of PBL migration in response to rIL-1 alpha and LTB4, but had no effect on the responses to rIL-2 and ZAP. These data provide evidence that CsA and dexamethasone are potent and selective inhibitors of in vitro lymphocyte migration, effects which may contribute to their therapeutic efficacy in vivo.