Table 1. Selected rodent models of inflammatory lung disease.

PowerPoint slide

Disease modelled	Technique	Strategy/basis for technique	Phenotype/cytokine expression	Advantage	Disadvantage	Outcome	References
IPF	Bleomycin lung injury	Known pulmonary toxi-city causing fibrosis in human cancer patients	T-cell-independent, CCL2 and 12 required, inflammatory cell recruitment, TGF-β	Well-known, characterized, quick (14–28 days), multiple routes of administration	Disease resolves in mice but not in humans. Variable response between mouse strains.	Dependent on time point (inflammation vs. fibrosis)	94, 96 and 97
	FITC	Direct chemical injury	T-cell-independent, inflammatory cell and fibrocyte recruitment, IL-13	Visualization as FITC deposition denoted by green immuno-fluorescence, persistent	Variable efficacy of dose	Lymphocyte-independent pulmonary fibrosis by day 21	93, 94
	Irradiation	Radiation injury	Monocyte/lymphocyte-derived lymphotactin, RANTES, CCL-2 and 7, CXCL-10, TGF-β	Different susceptibility of mouse strains allows genetic study	Slow (24 weeks)	Model of radiation fibrosis	93, 94
	Silica	Resistant, fibrogenic particles administered intratracheally	Inflammatory cell recruitment, IL-1, TNF-α, IL-10, TH2	Persistent	Specialized aerosolization equipment required (non-essential), lengthy (60 days)	Inflammatory injury followed by fibrosis after min 30 days	94
	Transgenic TGF-α	TGF-α increased in IPF patients’ BAL	TGF-α overexpression. Fibrosis without inflammation	Incisive single-cytokine system	Not representative of complexity of actual disease state	Pulmonary fibrosis at 4 days	98
	Adenovirus delivery of GMCSF, TNF, TGF-β, IL-1b	Overexpression of important cytokines	Various	Incisive single-cytokine system	As before, vigorous immune response to virus, epithelium trophic	Cytokine dependent	99, 100, 101 and 102
IPF and asthma	Transgenic IL-13	IL-13 elevated in IPF patients and asthmatics	IL-13, CCR1,-2,-5,-10, TGF-β,IL-11, MMP-1,VEGF	More complex-cytokine pattern	As above plus TH2 phenotype	Eosinophil-rich inflammation followed by fibrotic foci long term	103
Asthma	Ovalbumin/HDM/cockroach/ragweed sensitization	Allergen sensitization	TH2, IgE, eosinophilia, airway hyper-responsiveness	Models TH2 inflammatory response, quick	High-dose, infrequent exposure as opposed to low-dose frequent allergen exposure in human disease, eosinophils less likely to degranulate. Effective mouse therapies do not necessarily translate (e.g., anti-Il-5)	Eosinophilic inflammation	92, 104
COPD	Inhalation of smoke. Chronic smoke exposure	Smoking causative of COPD	Mild COPD (Gold 1,2)	Simple design. Relevant to etiology of disease in humans	Time-consuming, humans tend to have more advanced disease at presentation	Mild COPD model	105
	Neutrophil elastase KO mouse	Elastase a key neutrophil product	Smoke damage resistant	Incisive	Simplistic	59% protection from emphysema	74
	Variety of transgenic KO mice plus smoke exposure (MMP1,9,12,TNFR 1+2)	Relevance of MMPs in COPD development	Various	Examine importance of a single chemokine to COPD and smoke-related inflammation	Difficult technique requiring expertise.	KO dependent	106, 107
	α1-AT “Pallid mouse”	α1-AT deficiency predisposes to emphysema in humans	CD4+ cells significantly increased in tissue	Has human corollary in α1-AT deficiency phenotype	Small minority human COPD due to α1-AT deficiency	Panlobular emphysema	106, 107
	Itgb6 null mice	Alteration in TGF-β responsiveness	TGF-β deplete, MMP12 overactivity, age-dependent emphysema	Chronic progressive model	Complex	Age-dependent emphysema	106, 107
CF	CFTR gene knockouts (various, approx.11 models)	CF single-gene disease	Failed mucociliary clearance, inflammatory cell recruitment, parenchymal interstitial thickening, pseudomonal susceptibility	Multiple phenotypes generated by different CFTR mutations	Phenotypes not directly applicable to human genotypes	Various	91
ALI/ARDS	Hyperoxia	Exposure to 95% O2	TNF, IFN-γ, ROS,IL-12, IL-18	Quick	O2 chamber required,	Hyperoxic lung injury	108
	LPS IT	Sepsis associated with ARDS	ROS, NF-κB, IL-6, IL-8	Widely used, well-characterized	Overly simplistic	Model of sepsis-related ARDS/ALI	109
	Hemorrhage/resus lung injury	Venesection to shock +/−resus	CREB, ROS, NF-κB, IL-6, IL-8	Models clinical events	Technically difficult	Model of traumatic ARDS/ALI	110, 111
	Infective	Respiratory reovirus 1/L induction of diffuse alveolar damage	Overlapping phases of exudation including hyaline membranes, regeneration, and healing via resolution and or repair with fibrosis.	Fibro-reparative phase modeled as well as initial insult	Technically difficult	Neutrophilic inflammation	112

Abbreviations: ARDS/ALI, adult respiratory distress syndrome/acute lung injury; CF, cystic fibrosis; COPD, chronic obstructive pulmonary disease; IPF, idiopathic pulmonary fibrosis.