Effects of particulate matter on cytokine production in vitro: a comparative analysis of published studies

In recent years evidence has accumulated indicating that airborne particles cause adverse health effects. To understand the underlying mechanisms, a multitude of in vitro studies have been performed focusing on inflammatory responses, especially cytokine production. However, the diversity of studies renders it difficult to determine which results are consistent and which exposures most effective. The present review thus aimed to perform a comparative analysis of the available data. Forty-nine studies dealing with in vitro effects of particles on cytokine production in bronchial epithelial or related cells and monocytes/macrophages were included. Twenty-eight studies investigated epithelial cells and could be categorized according to specific combinations of exposure level and time, and 27 dealt with monocytes/macrophages. Eight studies provided further data using non-compatible exposure modes. The most common finding was that particles significantly induced cytokine production in both epithelial cells and monocytes/macrophages at concentrations of 50-100 microg/mL and exposure times of 9-24 h. The effects did not appear to be significantly different between cell or particle types. There were virtually no effects reported below 10 microg/mL, but these levels were used in only a few studies. Thus, the available data demonstrate that cytokine measurements are sensitive enough to assess cell activation after particle exposure in vitro, yielding relatively consistent results across cell types. However, since the majority of data refers to high particle load compared to in vivo conditions, future studies should consider more sensitive assays, multivariate panels describing the cell's regulatory state, interactions between cell types, and second-line outcome measures that are close to clinically observed effects.