Table. 1—

Summary of statin mediated pharmacological effects on pulmonary inflammation and remodeling

COPD pathwayStudy typeStatin effect on pathogenic pathways[Ref.]
Cytokine productionMM, HM in vitro (liver cell line), HM in vivo (mononuclear cells)Reduce IL-6 induced CRP production by hepatocytes[52, 67, 68]
HM in vitro (VSM cells and PBE cells)Reduce IL-8 production by VSM cells[69, 70]
MMInhibition of neutrophil accumulation and IL-8 and TNF-α concentration in BALF in rats[71]
HM in vivo (serum), MMReduce production of IL-β1 and TNF-α[52, 72]
MMReduced expression of IFN-γ TNF-α and MMP12 in whole lung[73]
Matrix remodellingMMReduced lung parenchymal destruction and MMP 9 activity in smoke exposed rat lung[74, 75]
HM ex vivo (bronchial epithelial cells)Reduce release of MMP2 and MMP9 from bronchial epithelial cells from lung transplant patients[70]
Neutrophil/macrophage influxHM ex vivo (bronchial epithelial cells), HM in vivo (PMN)Reduce neutrophil influx in lung transplant recipients by inhibiting release of IL-8 and GM-CSF from bronchial epithelial cells[70, 76, 77]
HM in vitro (PMN), HM in vivo (serum)Reduce neutrophil endothelial adhesion and transendothelial migration[76, 78–80]
MMReduce neutrophil influx and inhibit the development of elastase induced pulmonary emphysema in mice[74, 75]
MM, HM ex vivo (human monocytes)Reduce CRP-induced monocyte migration by inhibition of ICAM-1 in human monocytes[81]
MM, HM in vitro (endothelial cells), HM in vivo (BALF)Reduced concentration of neutrophils and lymphocytes in BALF[74, 75]
MM, HM in vitroReduce chemokine and adhesion molecule expression to reduce migration of inflammatory cells into the airways[74, 81, 82]
Epithelial/endothelial integrityMMPromotes alveolar cell regeneration and restores endothelial cell function[75]
MMReduce LPS-induced IL-6 gene expression leading to reduced lung vascular leak and pulmonary inflammation in mice lung[83]
HM in vitro (endothelial and smooth muscle cells)Inhibition of VEGF in smooth muscle cells and endothelial cells[84]
ApoptosisHM in vitro (macrophages and PMN)Enhances clearance of apoptotic cells in alveolar macrophages from patients with COPD[85]
HM in vitro (endothelial cells), HM in vitro (endothelial and smooth muscle cells)Increase apoptosis in human vascular endothelial cells[84, 86]
Oxidant responseHM in vivo (PMN)Reduce IL-8 release from neutrophils and neutrophil derived reactive oxidant species[77]
HM in vivo (serum), MMStrong anti-oxidant properties[87, 88]
Mucus productionMMReduced LPS-induced goblet cell hyperplasia in bronchial epithelium and Muc5A induced mucus hypersecretion[71]
CRP levelHM in vitro (liver cell)Reduce CRP levels at the transcriptional level thorough Rac-1 mediated inhibition of STAT3 phosphorylation[67]
  • COPD: chronic obstructive pulmonary disease; CRP: C-reactive protein; MM: murine model; HM: human model; VSM: vascular smooth muscle; PBE: primary bronchial epithelial; PMN: polymorphic neutrophil; BALF: bronchoalveolar lavage fluid; IL: interleukin; TNF: tumour necrosis factor; IFN: interferon; MMP: matrix metalloproteinase; GM-CSF: granulocyte-monocyte colony-stimulating factor; ICAM: intracellular adhesion molecule; LPS: lipopolysaccharide; VEGF: vascular endothelial growth factor.