Disease Models: Lung Models for Testing Drugs Against Inflammation and Infection
Lung diseases have increasingly attracted interest in the past years. The all-known fear of failing treatments against severe pulmonary infections and plans of the pharmaceutical industry to limit research on anti-infectives to a minimum due to cost reaso
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Contents 1 Introduction 2 Morpho-functional Characteristics of the Lung 3 Requirements to Model the Lung In Vitro 3.1 Technical Prerequisites 3.2 Sources of Cells 4 Modeling Pulmonary Diseases In Vitro 4.1 Asthma 4.2 Chronic Obstructive Pulmonary Disease (COPD) 4.3 Pulmonary Fibrosis 4.4 Bacterial Infections in the Context of Cystic Fibrosis and Pneumonia 4.5 Tuberculosis 5 Outlook References
Abstract
Lung diseases have increasingly attracted interest in the past years. The all-known fear of failing treatments against severe pulmonary infections and plans of the Patrick Carius and Justus C. Horstmann contributed equally to this work. P. Carius · J. C. Horstmann · C. de Souza Carvalho-Wodarz · C.-M. Lehr (*) Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research (HZI), Saarland University, Saarbrücken, Germany Department of Pharmacy, Saarland University, Saarbrücken, Germany e-mail: [email protected] # Springer Nature Switzerland AG 2020 Handbook of Experimental Pharmacology, https://doi.org/10.1007/164_2020_366
P. Carius et al.
pharmaceutical industry to limit research on anti-infectives to a minimum due to cost reasons makes infections of the lung nowadays a “hot topic.” Inhalable antibiotics show promising efficacy while limiting adverse systemic effects to a minimum. Moreover, in times of increased life expectancy in developed countries, the treatment of chronic maladies implicating inflammatory diseases, like bronchial asthma or chronic obstructive pulmonary disease, becomes more and more exigent and still lacks proper treatment. In this chapter, we address in vitro models as well as necessary in vivo models to help develop new drugs for the treatment of various severe pulmonary diseases with a strong focus on infectious diseases. By first presenting the essential handson techniques for the setup of in vitro models, we intend to combine these with already successful and interesting model approaches to serve as some guideline for the development of future models. The overall goal is to maximize time and cost-efficacy and to minimize attrition as well as animal trials when developing novel anti-infective therapeutics. Keywords
Air-blood barrier · Air-liquid interface (ALI) · Biofilm · Cystic fibrosis · Deposition · Mycobacterium tuberculosis · Pseudomonas aeruginosa · Transepithelial electrical resistance (TEER) · Tuberculosis
Abbreviations ALI AT-I/AT-II CF CFBE41oCFTR COPD ECM EMA FDA hAELVi hAEpCs IPF LCC LPS NHBE PQS TB TEER
Air-liquid interface Alveolar type I/II pneumocytes Cystic fibrosis Cystic fibrosis human bronchial epithelial cells Cystic fibrosis transmembrane conductance regulator Chronic obstructive pulmonary disease Extracellular matrix European Medicines Agency Federal Drug Administration Human alveolar epithelial lentivirus immortalized Human alveolar epithelial cells Idiopathic pulmonary fibrosis Liquid-covered conditions Lipopolysaccharide Normal human bronchial epithelial cells Pseudomonas quinolone signal Tuberculosis Transep
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