Pentoxifylline potentiates in vitro lymphocyte suppression by glucocorticoids and immunosuppressive drugs

Abstract

Pentoxifylline, which has immunomodulatory effects in addition to its better known rheologic effects, might potentiate the effectiveness of traditional immunosuppressive drugs. We therefore studied the suppressive effect of pentoxifylline in combination with clinically relevant concentrations of prednisolone, methylprednisolone, cyclosporine, tacrolimus, rapamycin, and mycophenolic acid on mitogen-stimulated lymphocytes from 29 patients with glomerular diseases. Inhibition of lymphocyte proliferation obtained with 10(-7) and 10(-8) mol/L concentrations of the glucocorticoids and with 300 ng/mL cyclosporine was significantly increased when each was combined with 5, 25, or 50 microg/mL of pentoxifylline. The additive inhibitory effect of pentoxifylline in combination with 10(-7) mol/L glucocorticoids was inversely proportional to the inhibitory effect of the 10(-7) mol/L concentration of glucocorticoid alone, suggesting that the less sensitive the patient's cells, the greater the potentiation by pentoxifylline. The greatest degree of potentiation by pentoxifylline occurred when combined with the lower (10(-8) mol/L) concentration of glucocorticoids. Pentoxifylline also significantly increased lymphocyte suppression in combination with 150 and 300 ng/mL concentrations of cyclosporine, 5 ng/mL of tacrolimus, 2.5 x 10(-7) mol/L mycophenolic acid, and 10 ng/mL of rapamycin. These in vitro results suggest that pentoxifylline might have steroid-sparing effects and contribute to improved clinical outcomes from immunosuppressive treatment of renal diseases.