Table. 1—

Summary of statin mediated pharmacological effects on pulmonary inflammation and remodeling

COPD pathway	Study type	Statin effect on pathogenic pathways	[Ref.]
Cytokine production	MM, 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]
	MM	Inhibition of neutrophil accumulation and IL-8 and TNF-α concentration in BALF in rats	[71]
	HM in vivo (serum), MM	Reduce production of IL-β1 and TNF-α	[52, 72]
	MM	Reduced expression of IFN-γ TNF-α and MMP12 in whole lung	[73]
Matrix remodelling	MM	Reduced 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 influx	HM 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]
	MM	Reduce 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 vitro	Reduce chemokine and adhesion molecule expression to reduce migration of inflammatory cells into the airways	[74, 81, 82]
Epithelial/endothelial integrity	MM	Promotes alveolar cell regeneration and restores endothelial cell function	[75]
	MM	Reduce 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]
Apoptosis	HM 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 response	HM in vivo (PMN)	Reduce IL-8 release from neutrophils and neutrophil derived reactive oxidant species	[77]
	HM in vivo (serum), MM	Strong anti-oxidant properties	[87, 88]
Mucus production	MM	Reduced LPS-induced goblet cell hyperplasia in bronchial epithelium and Muc5A induced mucus hypersecretion	[71]
CRP level	HM 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.