In vitro assessment of alveolar macrophage responses to inhaled particulate medicines

Lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) are an increasing global health burden affecting hundreds of millions of people worldwide. Despite considerable investment to develop new inhaled drugs, in recent years there has been limited success, in part due to the observation of foamy macrophage responses in rat studies which questions their safety for use in humans. The aim of this work was to use in vitro cell culture models of rat and human alveolar macrophages to better characterise the biological response of these airway immune cells to particulate medicines. U937 (human) and NR8383 (rat) macrophage models were dosed up to 24 h with 0.01 – 100 mg/ml of amiodarone, salbutamol or salmeterol in cell culture medium. Cells were assessed for a variety of responses including toxicity, induction of phospholipidosis, cytokine and chemokine production, cell signalling pathways and production of volatile organic compounds. No significant difference (p