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Statins Directly Suppress Cytokine Production in Murine Intraepithelial Lymphocytes

Statins Directly Suppress Cytokine Production in Murine Intraepithelial Lymphocytes

Jiong Zhang, Satoshi Osawa, Yasuhiro Takayanagi, Mutsuhiro Ikuma, Takanori Yamada, Mitsushige Sugimoto, Takahisa Furuta, Hiroaki Miyajima, Ken Sugimoto

Cytokine. 2013 Feb;61(2):540-5.

PMID: 23290865

Abstract:

Statins, inhibitors of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are known not only as cholesterol-lowering agents but also as anti-inflammatory mediators. However, their regulatory effect on intestinal mucosal immunity remains unclear. The present study examined the possible direct effects of statin on intestinal intraepithelial lymphocytes (IELs), the front line cells of the intestinal mucosal immune system. Murine IELs were isolated from the small intestines of C57BL/6 mice. IELs activated with anti-CD3/CD28 monoclonal antibodies produced interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, and IL-4 in significant numbers; however, they did not produce IL-5. Both simvastatin and lovastatin suppressed IEL production of IFN-γ, TNF-α, IL-2, and IL-4 in a dose-dependent manner, whereas 48-h treatment with high concentrations (5 × 10(-5)M) of simvastatin and lovastatin did not affect the number of IELs. The suppressive effect of the simvastatin was significantly restored by the addition of mevalonate, farnesyl pyrophosphate ammonium salt, and geranylgeranyl pyrophosphate ammonium salt, which are downstream metabolites of HMG-CoA. These findings suggest that statins have direct suppressive effects on the production of T helper 1-cytokines and IL-4 in IELs; these effects are associated with inhibition of the mevalonate pathway to some extent.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
ALP6699203	Geranylgeranyl pyrophosphate ammonium salt		6699-20-3 (free acid)	Price

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