Effects of various statins on cytokine-dependent growth and IgE-dependent release of histamine in human mast cells.
BACKGROUND
Statins are inhibitors of hydroxymethylglutaryl coenzyme A (HMG CoA) reductase, a key enzyme in mevalonic acid (MVA)-dependent signaling. Recent data suggest that statins exhibit profound inhibitory effects on growth and function of various immune cells. In the present study, we examined the in vitro effects of five different statins on primary human mast cells (MCs), MC progenitors, and the human MC line HMC-1.


METHODS
Histamine release experiments were conducted on isolated MCs using statins and an anti-immunoglobulin E (IgE) antibody. Culture experiments were performed with stem cell factor (SCF) and interleukin (IL)-6, and cord blood-derived progenitors.


RESULTS
Preincubation of primary lung MCs with cerivastatin or atorvastatin (1-50 microM) for 24 h resulted in inhibition of anti-IgE-induced release of histamine. The effects of both statins were dose-dependent. Moreover, both statins, and to a lesser degree lovastatin, were found to inhibit the SCF-induced differentiation of MCs from their progenitors. The other statins tested (simvastatin, pravastatin) did not affect mediator release or growth of MCs.


CONCLUSIONS
Cerivastatin and atorvastatin act as inhibitors of growth and function of human MCs.
Krauth
M T
MT
Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.
Majlesi
Y
Y
Sonneck
K
K
Samorapoompichit
P
P
Ghannadan
M
M
Hauswirth
A W
AW
Baghestanian
M
M
Schernthaner
G H
GH
Worda
C
C
Müller
M R
MR
Sperr
W R
WR
Valent
P
P
D017209:Apoptosis / Q000187:drug effects; D000069059:Atorvastatin; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006538:Heptanoic Acids / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007073:Immunoglobulin E / Q000187:drug effects / Q000378:metabolism*; D008148:Lovastatin / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology; D011336:Probability; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D012680:Sensitivity and Specificity
D016207:Cytokines; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011725:Pyridines; D011758:Pyrroles; D007073:Immunoglobulin E; D008148:Lovastatin; D000069059:Atorvastatin; C086276:cerivastatin