HMG-CoA reductase inhibitors deplete circulating classical and non-classical monocytes following human heart transplantation.
BACKGROUND
Monocytes mediate immune responses following solid organ transplantation via cytokine secretion and differentiation to macrophage/dendritic cell lineages. To date, the pleiotropic immunomodulatory effect of statins on human monocytes following human heart transplantation has yet to be elucidated. This study was designed to assess the effects of statin administration on the monocyte repertoire.


METHODS
108 patients were recruited into the study. Clinical data were collected from patients' notes. Peripheral blood immunophenotype was determined via flow cytometry (using CD11c, CD14, CD16, CD49d, CD64, CD80 and CD195).


RESULTS
There were fewer circulating classical (p=0.0001) and non-classical (p=0.0013) monocytes in patients treated with a statin. CD64 expression was down-regulated (p=0.011 and p=0.049) whereas CD49d expression was up-regulated (p=0.004 and p=0.022) on classical and non-classical monocytes in this group. Patients receiving Atorvastatin had fewer circulating classical monocytes (p=0.001) compared to patients administered Pravastatin. Patients receiving Pravastatin had fewer circulating non-classical monocytes (p=0.029) compared to patients administered Atorvastatin.


CONCLUSIONS
Statin administration alters the circulating monocyte repertoire following heart transplantation, including population size, FcgammaRI and VLA-4 adhesion molecule expression. Furthermore, different statin treatments are associated with a selective depletion of macrophage or DC (re)generating monocytes.
Fildes
J E
JE
The Transplant Centre, University Hospital of South Manchester NHS Foundation Trust, Manchester, M23 9LT, UK. james.fildes@manchester.ac.uk
Shaw
S M
SM
Mitsidou
A
A
Rogacev
K
K
Leonard
C T
CT
Williams
S G
SG
Yonan
N
N
D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D003430:Cross-Sectional Studies; D015536:Down-Regulation; D005260:Female; D016027:Heart Transplantation / Q000276:immunology*; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D039441:Integrin alpha4 / Q000276:immunology / Q000378:metabolism*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D017035:Pravastatin / Q000494:pharmacology / Q000627:therapeutic use; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D017452:Receptors, IgG; D039441:Integrin alpha4; D000069059:Atorvastatin; D017035:Pravastatin