Molecular mechanisms underlying inflammatory lung diseases in the elderly: Development of a novel therapeutic strategy for acute lung injury and pulmonary fibrosis

In the elderly, inflammatory lung diseases, including acute lung injury and pulmonary fibrosis, are significant in terms of both mortality and difficulty in management. Acute respiratory distress syndrome (ARDS) is an acute lung injury and the mortality rate for ARDS ranges from 40 to 70% despite intensive care. Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disorder of the lung parenchyma. No useful drugs are currently available to treat IPF. However, molecular mechanisms underlying these lung diseases are little understood and the development of a novel therapeutic strategy is urgently needed. Platelet‐activating factor (PAF) and metabolites of arachidonic acid, i.e. eicosanoids, are lipid mediators that have various biological effects. A key enzyme for the production of these inflammatory mediators, including eicosanoids and PAF, is phospholipase A 2 . In particular, cytosolic PLA 2 (cPLA 2 ) is especially important. The purpose of this article is to report novel findings regarding the role of PAF and cPLA 2 in lung inflammatory diseases, especially, acute lung injury and pulmonary fibrosis. To address this question, we used mutant mice, i.e. PAFR transgenic mice, PAFR gene‐disrupted mice and cPLA 2 gene‐disrupted mice. We have shown that PAF and eicosanoids, downstream mediators of cPLA 2 , may be involved in the pathogenesis of ARDS and IPF, which are important diseases in the elderly. Although there exist extreme differences in clinical features between ARDS and IPF, both diseases are fatal disorders for which no useful drugs are currently available. On the basis of recent reports using mutant mice, cPLA 2 might be a potential target to intervene in the development of pulmonary fibrosis and acute lung injury in the elderly.