Prednisolone suppresses the function and promotes apoptosis of plasmacytoid dendritic cells.
Organ transplant recipients are highly susceptible to viral infections early after transplantation. Plasmacytoid dendritic cells (PDC) play a major role in antiviral immunity. Therefore, we determined the numbers of circulating PDC after liver transplantation (LTX) and established the effects of immunosuppressive drugs on PDC survival and function. PDC were determined longitudinally in 13 LTX recipients treated with prednisone and cyclosporin or tacrolimus. Purified PDC were cultured with or without clinically relevant concentrations of cyclosporin, tacrolimus or prednisolone. Apoptosis induction was monitored by determination of active caspase-3, nuclear condensation and annexin-V/7AAD staining. After LTX, a 4-fold reduction in the number of circulating PDC was observed (p < 0.01), which recovered partially after discontinuation of prednisone treatment. In vitro, prednisolone induced apoptosis in PDC, while cyclosporin and tacrolimus did not. Higher doses of prednisolone were needed to induce apoptosis in Toll-like receptor (TLR)-stimulated PDC. However, non-apoptosis inducing concentrations of prednisolone suppressed interferon-alpha production, upregulation of co-stimulatory molecules and allo-stimulatory capacity of TLR-stimulated PDC. In conclusion, prednisolone induces apoptosis in PDC, which explains the decline in circulating PDC numbers after transplantation. Moreover, prednisolone suppresses the functions of TLR-stimulated PDC. Therefore, corticosteroid-free immunosuppressive therapy may reduce the number and severity of viral infections after transplantation.
Boor
P P C
PP
Department of Gastroenterology and Hepatology, Erasmus MC- University Medical Center, Rotterdam, The Netherlands.
Metselaar
H J
HJ
Mancham
S
S
Tilanus
H W
HW
Kusters
J G
JG
Kwekkeboom
J
J
D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000627:therapeutic use*; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011239:Prednisolone / Q000627:therapeutic use*; D011379:Prognosis; D012189:Retrospective Studies; D014777:Virus Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control
D005938:Glucocorticoids; D011239:Prednisolone