Targeting defective pulmonary innate immunity – A new therapeutic option?

Publication date: Available online 13 February 2020Source: Pharmacology & TherapeuticsAuthor(s): Kylie B.R. Belchamber, Louise E. DonnellyAbstractChronic pulmonary conditions now account for 1 in 15 deaths in the US and mortality is increasing. Chronic obstructive pulmonary disease (COPD) is due to become the 3rd largest cause of mortality by 2030 and mortality from other respiratory conditions such as asthma, idiopathic pulmonary fibrosis and cystic fibrosis are not reducing. There is an urgent need for novel therapies to address this problem as many of the current strategies targeting inflammation are not sufficient. The innate immune system of the lung is an important defence against invading pathogens, but in many chronic pulmonary diseases, this system mounts an inappropriate response. In COPD, macrophages are increased in number, but fail to clear pathogens correctly and become highly activated. This leads to increased damage and remodelling of the airways. In idiopathic fibrosis, there is a switch of macrophage phenotype to a cell that promotes abnormal repair. Neutrophils also display dysfunction in COPD where aberrant migratory profiles may lead to increased damage to lung tissue and emphysema; while in cystic fibrosis the proteolytic lung environment damages neutrophil receptors leading to ineffective phagocytosis and migration. Targeting the innate immune system to restore ‘normal function’ could have enormous benefits. Improving phagocytosis of pathogens could...

Source: Pharmacology and Therapeutics - February 13, 2020 Category: Drugs & Pharmacology Source Type: research