Intolerance of bromocriptine: is metergoline a satisfactory alternative?

Abstract

Adverse health outcomes associated with particulate matter (PM) exposure are established, yet the mechanistic toxicology relating to their inhalation hazard is less known. In vitro lung systems are a vital model to attain this, though are required to closely mirror human exposures. Thus, methods adopted must be characterised and realistic. Initial studies have compared a nebulised aerosol (VitroCell® ‘Cloud’) and liquid suspension (quasi-air liquid interface (qALI)) exposure methods in lung models comprising alveolar type II cells and macrophages. Printex® 90 Carbon Black (CB) was used as a model particle at deposited concentrations 390, 780, 3,100 ng/cm2 with the Cloud system, and comparable qALI concentrations of 1.64, 3.28, 13.04 µg/ml for 24 hrs. After Cloud exposure, while monocultures showed a non-significant (p>0.05) stepwise concentration dependent decrease in viability (trypan blue exclusion assay), the trend reached significance (p<0.05) in epithelial_macrophage cell co-cultures. qALI exposures did not significantly (p>0.05) affect viability. An ELISA detected presence of IL-6 in epithelial but not macrophage cell supernatant, and was unchanged following CB exposure in either system. qALI exposures caused a non-significant (p>0.05) concentration dependent decrease in IL-8 secretion, potentially through absorption by CB but was unchanged following Cloud exposures. Variation between the systems shows exposure method clearly affects observed cytotoxicity and immune response. Thus, consideration must be made when conducting PM exposure studies in vitro regarding suitability of the specific models and exposure approaches used.