Reassuring effect of pravastatin on natural killer cell activity in stable renal transplant patients.
BACKGROUND
Administration of pravastatin soon after transplantation successfully lowers cholesterol levels, whereas a reduced number of acute rejection episodes is accompanied by a decrease in natural killer (NK) cell activity. As a consistent low NK cell activity caused by pravastatin might impair tumor surveillance leading to cancer, we studied the effect of pravastatin on NK cell activity in stable renal transplant patients.


METHODS
From 14 cyclosporine (CsA)-treated and 11 azathioprine (AZA)-treated patients with hypercholesterolemia, more than 1 year after kidney transplantation, we determined NK cell number and cytotoxic activity before, and at 6 and 12 weeks after, initiating pravastatin treatment. Additionally, cholesterol levels and liver and kidney function parameters were assessed.


RESULTS
During pravastatin treatment, total cholesterol and low-density lipoprotein-cholesterol levels decreased significantly in both patient groups. In the CsA group, the number and cytotoxic activity of the NK cells at 12 weeks after institution of pravastatin was in the same range as before pravastatin. Additionally, in the AZA group, pravastatin did not influence the number of NK cells. However, in the AZA group, both the number of NK cells and their cytotoxic activity were significantly (<0.002) lower compared to the values in the CsA group.


CONCLUSIONS
In contrast to previous reports on decreased NK cell cytotoxicity caused by pravastatin treatment early after transplantation, we cannot confirm these results in stable kidney recipients. In our hands, NK cell cytotoxicity during pravastatin treatment was within the same range as in the absence of pravastatin. Thus, in view of the potential role of NK cells in tumor surveillance, these data are reassuring.
Vaessen
L M
LM
Department of Internal Medicine, University Hospital Rotterdam-Dijkzigt, The Netherlands. vaessen@inw1.azr.nl
van Miert
P P
PP
van Gelder
T
T
Ijzermans
J N
JN
Weimar
W
W
D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D016572:Cyclosporine / Q000627:therapeutic use; D003602:Cytotoxicity, Immunologic; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D020014:K562 Cells; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000276:immunology* / Q000502:physiology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D007958:Leukocyte Count; D008111:Liver Function Tests; D018655:Lymphocyte Count; D011183:Postoperative Complications; D017035:Pravastatin / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D007166:Immunosuppressive Agents; D014280:Triglycerides; D016572:Cyclosporine; D002784:Cholesterol; D017035:Pravastatin; D001379:Azathioprine