Immunosuppressant pharmacodynamics on peripheral-blood mononuclear cells from patients with ulcerative colitis

Cellular pharmacodynamics of immunosuppressive drugs for individualized medicine

“…PBMC-responses to immunosuppressive drugs exhibit wide individual variations in ulcerative colitis (UC) patients [89]. The variability in IC 50 values for immunosuppressive drugs including GCs in UC is similar to those reported in renal transplant recipients and asthma patients [16,73], where individual differences in IC 50 values of immunosuppressive drugs were reported to be 10 3-4 folds.…”

“…UC patients exhibiting low PBMC-sensitivity to prednisolone have been reported to require high prednisolone doses as well as long periods of prednisoloneadministration for treatment [89]. The incidences of UC patients exhibiting PBMC-resistance to GC and cyclosporine were significantly higher than those of healthy subjects [89]. These subjects might have a high risk of being refractory to the therapy based on these drugs, as has been suggested by Hearing et al [19].…”

“…The variability in IC 50 values for immunosuppressive drugs including GCs in UC is similar to those reported in renal transplant recipients and asthma patients [16,73], where individual differences in IC 50 values of immunosuppressive drugs were reported to be 10 3-4 folds. UC patients exhibiting low PBMC-sensitivity to prednisolone have been reported to require high prednisolone doses as well as long periods of prednisoloneadministration for treatment [89]. The incidences of UC patients exhibiting PBMC-resistance to GC and cyclosporine were significantly higher than those of healthy subjects [89].…”

Bacterial superantigen TSST-1 attenuates suppressive efficacy of glucocorticoids and calcineurin inhibitors against blastogenesis of peripheral blood mononuclear cells from patients with antineutrophil cytoplasmic antibody-associated vasculitis and nephrosis

“…The suppressive efficacy of prednisolone against blastogenesis of PBMCs stimulated with con A in ANCA patients with higher serum MPO-ANCA levels was significantly diminished, as compared to the efficacy in patients with relatively lower serum MPO-ANCA levels. It has been reported that the in vitro response of con A-stimulated PBMCs to the suppressive effects of glucocrticoids is correlated with the therapeutic efficacy of the drugs in renal transplantation and asthma [5,[7][8][9][10]. The present data thus raise the possibility that patients exhibiting high levels of MPO-ANCA are refractory to prednisolone therapy.…”

“…One of the attractive ways to predict the clinical efficacy of immunosuppressive drugs in individual patients is the cellular pharmacodynamics of drugs using PBMCs of patient origin [4][5][6]. It has been reported that the in vitro response of PBMCs to the suppressive effects of immunosuppressive drugs correlate with clinical efficacy in asthma [7], renal transplantation [5,8], minimal change nephrotic syndrome [5,6], psoriasis [4], rheumatoid arthritis [9], and ulcerative colitis [10]. We have also revealed a large individual differences in the PBMC-suppressive effects of glucocorticoids, cyclosporine and tacrolimus between patients, and that patients with PBMCs exhibiting poor response to the drugs in vitro also show low responses to the clinical efficacy of the drugs [4,8,11,12].…”