How Lipitor and Crestor damage the body's immune system by inhibiting human mast cells

Human mast cells are a part of the body's immune system. (e.g., see
Wickipedia "A mast cell (or mastocyte) is a resident cell of connective
tissue that contains many granules rich in histamine and heparin. Although
best known for their role in allergy and anaphylaxis, mast cells play an
important protective role as well, being intimately involved in wound
healing and defense against pathogens."
http://en.wikipedia.org/wiki/Mast_cell

Statins, particularly Lipitor and Crestor, interfere with this protection:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16436135&query_hl=11&itool=pubmed_DocSum

Allergy. 2006 Mar;61(3):281-8.

Effects of various statins on cytokine-dependent growth and IgE-dependent
release of histamine in human mast cells.

Krauth MT, Majlesi Y, Sonneck K, Samorapoompichit P, Ghannadan M, Hauswirth
AW, Baghestanian M, Schernthaner GH, Worda C, Muller MR, Sperr WR, Valent P.

Department of Internal Medicine I, Division of Hematology and
Hemostaseology, Medical University of Vienna, Vienna, Austria.

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 muM) 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.

PMID: 16436135 [PubMed - in process]


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