Systematic review of preclinical studies on the neutrophil-mediated immune response to air pollutants, 1980–2020

Preclinical evidence about the neutrophil-mediated response in exposure to air pollutants is scattered and heterogeneous. This has prevented the consolidation of this research field around relevant models that could advance towards clinical research. The purpose of this study was to systematic review the studies of the neutrophils response to air pollutants, following the recommendations of the Cochrane Collaboration and the PRISMA guide, through 54 search strategies in nine databases. We include 234 studies (in vitro, and in vivo), being more frequent using primary neutrophils, Balb/C and C57BL6/J mice, and Sprague-Dawley and Wistar rats. The most frequent readouts were cell counts, cytokines and histopathology. The temporal analysis showed that in the last decade, the use of mice with histopathological and cytokine measurement have predominated. This systematic review has shown that study of the neutrophils response to air pollutants started 40 years ago, and composed of 100 different preclinical models, 10 pollutants, and 11 immunological outcomes. Mechanisms of neutrophils-mediated immunopathology include cellular activation, ROS production, and proinflammatory effects, leading to cell-death, oxidative stress, and inflammatory infiltrates in lungs. This research will allow consolidating the research efforts in this field, optimizing the study of causal processes, and facilitating the advance to clinical studies.