Attenuation of airway inflammation by simvastatin and the implications for asthma treatment: is the jury still out?

Abstract

Although some studies have explained the immunomodulatory effects of statins, the

exact mechanisms and the therapeutic significance of these molecules remain to be

elucidated. This study not only evaluated the therapeutic potential and

inhibitory mechanism of simvastatin in an ovalbumin (OVA)-specific asthma model

in mice but also sought to clarify the future directions indicated by previous

studies through a thorough review of the literature. BALB/c mice were sensitized

to OVA and then administered three OVA challenges. On each challenge day, 40 mg

kg(-1) simvastatin was injected before the challenge. The airway responsiveness,

inflammatory cell composition, and cytokine levels in bronchoalveolar lavage

(BAL) fluid were assessed after the final challenge, and the T cell composition

and adhesion molecule expression in lung homogenates were determined. The

administration of simvastatin decreased the airway responsiveness, the number of

airway inflammatory cells, and the interleukin (IL)-4, IL-5 and IL-13

concentrations in BAL fluid compared with vehicle-treated mice (P<0.05).

Histologically, the number of inflammatory cells and mucus-containing goblet

cells in lung tissues also decreased in the simvastatin-treated mice. Flow

cytometry showed that simvastatin treatment significantly reduced the percentage

of pulmonary CD4(+) cells and the CD4(+)/CD8(+) T-cell ratio (P<0.05).

Simvastatin treatment also decreased the expression of the vascular cell adhesion

molecule 1 and intercellular adhesion molecule 1 proteins, as measured in

homogenized lung tissues (P<0.05) and human epithelial cells. The reduction in

the T cell influx as a result of the decreased expression of cell adhesion

molecules is one of the mechanisms by which simvastatin attenuates airway

responsiveness and allergic inflammation. Rigorous review of the literature

together with our findings suggested that simvastatin should be further developed

as a potential therapeutic strategy for allergic asthma.