Table 2– Effect of matrix metalloproteinase (MMP) inhibitors in different lung pathologies

Lung pathology		MMP inhibitor	Species	Observations	[Ref.]
COPD	Cigarette smoke	RS113456	Mice	Reduced neutrophil but not macrophage infiltration	[46]
	Cigarette smoke	PKF242-484	Mice	Reduced neutrophilia in BALB/C mice; no effects in C57BL/6 mice	[47]
	Cigarette smoke	Ilomastat GM6001	Mice	Reduced emphysema and inflammation	[48, 49]
	Cigarette smoke	CP 471,474	Guinea pigs	Delayed emphysema	[50]
	Cigarette smoke	AZ11557272	Mice	Reduced emphysema, inflammatory cell numbers and desmosine levels in BALF and TNF serum levels, reverted smoke-induced airspace enlargement	[51]
	Cigarette smoke	AS112108	Mice	Dampened early inflammatory process and inhibited increase in neutrophil numbers	[52]
	Cigarette smoke	AS111793	Mice	Dose-dependent reduction of the increase in the number of neutrophils and macrophages in BALF and the levels of several inflammation markers	[53]
	rhMMP12	MMP408	Mice	Reduced lung inflammation	[54]
	Acrolein	Doxycycline	Mice	Attenuation of mucin synthesis	[55]
Asthma	OVA	R-94138	Mice	Reduced development of allergic airway inflammation	[56]
	Dermatophagoides pteronyssinus	Marimastat	Human	Reduced bronchial hyperresponsiveness	[57]
	OVA	GM6001	Mice	Dose-dependent inhibition of inflammatory cell egression with concomitant accumulation of inflammatory cells in the lung parenchyma	[21]
	TDI	MMPI-I	Mice	Decreased number of inflammatory cells in BALF	[58, 59]
	TDI	MMPI-II	Mice	Decreased number of inflammatory cells in BALF	[59]
	OVA	C₂₇H₃₃N₃O₅S	Mice	Decreased severity of eosinophilic inflammation	[60]
	Ascaris suum	MMP408	Sheep	Inhibited early and late airway responses	[61, 62]
	OVA	S-1 (N-sulfonylamino acid derivative)	Mice	Inhibited increase in eosinophils in the BALF	[63]
	OVA	C₁₇H₁₈N₂O₅S	Mice	Reduced recruitment of Th cells and decreased severity of eosinophilic inflammation	[60]
	OVA	TIMP1	Mice	Reduced development of allergic asthma	[56]
	OVA	TIMP2	Mice	Reduced development of allergic asthma	[56]
ILD	Bleomycin	Batimastat	Mice	Reduced development of fibrosis	[64]
ALI	I/R	Ilomastat	Mice	Attenuated lung inflammation and injury	[65]
	Oleic acid	Ilomastat	Mice	Attenuated lung inflammation and injury	[65]
	I/R	ONO-4817	Mice	Attenuated lung injury	[66]
	LPS	COL-3	Yorkshire pigs	Attenuated lung injury	[67]
	High-pressure ventilation	Phosphonate derivative	Mice	Better gas exchange	[30]
				Decreased lung oedema and permeability
				Diminished histological damage
	Ventilation	CMT-3	Mice	Reduced neutrophilic inflammation	[68]
	Pancreatitis	Doxycycline	Mice	Reduced lung injury	[69]
Lung cancer	B16-F10 melanoma cells	MMI270	Mice	Decreased number of lung colonies	[70]
	NSCLC	BMS-275291	Human	No improvement in survival	[71]
	N-Nitrosodimethylamine	BAY 12-9566	Mice	Reduced neoplastic growth and development	[72]
	MMTV-PyMT	GM6001	Mice	Anti-metastatic effects	[73]
	MMTV-PyVT	SB-3CT	Mice	Huge decrease in lung tumour burden	[40]
	A549 cells	Ad-MMP2-si	Mice	Decreased tumour growth	[74]
	Lewis lung carcinoma	CH1104I	Mice	Inhibited pulmonary metastasis	[75]
BOS	Lung I/R	COL-3	Rats	Improved oxygenation	[76]
	Lung I/R		Rats	Diminished polymorphonuclear leukocyte influx into the isograft	[76]
	Lung transplantation		Rats	Suppression of delayed type hypersensitivity responses	[77]
				Abrogated local cytokine production
				No prevention of rejection pathology

COPD: chronic obstructive pulmonary disease; ILD: interstitial lung diseases; ALI: acute lung injury; BOS: bronchiolitis obliterans syndrome; BALF: bronchoalveolar lavage fluid; TNF: tumour necrosis factor; OVA: ovalbumin; TDI: toluene diisocyanate-induced; Th: T-helper; TIMP: tissue inhibitor of metalloproteinases; I/R: ischaemia/reperfusion; LPS: lipopolysaccharide; CMT-3, COL-3: chemically modified tetracycline 3; NSCLC: nonsmall cell lung carcinoma; MMTV-PyMT, MMTV-PyVT: mouse mammary tumour virus with polyoma middle T-antigen promoter, mouse mammary tumour virus; Ad-MMP2-si: adenoviral MMP2 siRNA.