Sirolimus inhibits oxidative burst activity in transplant recipients

Gee, I; Trull, AK; Charman, SC; Alexander, GJ; (2003) Sirolimus inhibits oxidative burst activity in transplant recipients. Transplantation, 76 (12). pp. 1766-8. ISSN 0041-1337 DOI:

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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.

Item Type: Article
Keywords: Adult, Female, Humans, Immunosuppressive Agents/therapeutic use, Kidney Transplantation/*immunology, Liver Transplantation/*immunology, Male, Middle Aged, Reference Values, Respiratory Burst/*drug effects, Sirolimus/*therapeutic use, Tetradecanoylphorbol Acetate/pharmacology, Adult, Female, Humans, Immunosuppressive Agents, therapeutic use, Kidney Transplantation, immunology, Liver Transplantation, immunology, Male, Middle Aged, Reference Values, Respiratory Burst, drug effects, Sirolimus, therapeutic use, Tetradecanoylphorbol Acetate, pharmacology
Faculty and Department: Faculty of Public Health and Policy > Dept of Health Services Research and Policy
PubMed ID: 14688530
Web of Science ID: 187578400020


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