Sirolimus inhibits oxidative burst activity in transplant recipients

Increased susceptibility to bacterial infection is a recognized side-effect of sirolimus treatment after transplantation, which could be caused by inhibition of neutrophil activation. Blood from 24 healthy subjects was equilibrated with 0 to 50 ng/mL sirolimus or 60 microg/mL propofol. Blood was also collected from 23 transplant recipients (13 kidney, 10 liver) with renal impairment, randomized to remain on calcineurin inhibitors (n=12) or to be switched to sirolimus monotherapy (n=11). Phorbol myristate acetate (PMA)-stimulated oxidative burst was measured by flow cytometry at 0 and 3 months after randomization. There was a linear relationship between inhibition of neutrophil activation in vitro and sirolimus concentrations spanning the therapeutic range (P=0.01). Neutrophil activation was decreased significantly in transplant recipients 3 months after switching from calcineurin inhibitors to sirolimus therapy (mean percentage change -24.4%; 95% confidence interval -7.5, -41.2%, P=0.009), but no changes were observed in patients who remained on calcineurin inhibitors.