Atorvastatin lowers inflammatory sputum mediators in smokers with asthma

Statins have immunomodulatory effects that may be beneficial in the treatment of asthma. We studied the effects of atorvastatin alone and in combination with inhaled beclometasone (ICS) on a range of sputum supernatant mediator concentrations from samples of a clinical trial that reported asthma control score improvements after short-term treatment with atorvastatin (Braganza G et al, BMC Pulm Med 2011). 39 samples were analysed for concentrations of 35 mediators (Luminex or biochemical analyses) implicated in asthma pathogenesis and their relationship with control scores. No marker was found to be reduced by ICS alone. Markers of inflammation, neutrophil function and remodelling pathways were reduced by the treatments: CCL7, IL-12p70, sCD40L, FGF-2, CCL4, TGF-α, and MMP-8 by atorvastatin as compared to placebo; MMP-8, IL-1β, IL-10, MMP-9, sCD40L, FGF-2, IL-7, G-CSF and CCL7 by atorvastatin + ICS as compared to ICS alone. Correlation analyses showed that a reduction in sputum neutrophil count was associated with a decrease in IL-6 [0.639 (0.286, 0.839), p=0.001 ] and CXCL8 [0.541 (0.153, 0.784), p=0.007 ] after atorvastatin treatment. After atorvastatin + ICS treatment, an improvement in ACQ score was associated with a reduction in sputum CCL2 [0.542 (0.165, 0.780), p=0.006 ] and CXCL8 [0.513 (0.126, 0.764), p=0.010 ], while an improvement in AQLQ score was associated with a reduction in CXCL8 [-0.572 (-0.797, -0.207), p=0.003 ], G-CSF [-0.543, (-0.781, 0.167), p=0.006 ] and IL-7 [-0.533 (-0.776, -0.154), p=0.007 ]. This combined data suggests that atorvastatin may affect markers of neutrophil function and airway remodelling in chronic asthma. Further long-term clinical studies are needed to elucidate these effects.