Importance of soluble metals and reactive oxygen species for cytokine release induced by mineral particles

The mechanisms for particle-induced health effects are not well understood, but inflammation seems to be of importance. Previously, we have shown that stone quarry particles with various mineral and metal content differed widely in potency to induce inflammatory cytokines (IL-6, IL-8 and TNF-α) in different types of lung cells. In this study we investigated if the observed cytokine responses were associated with the soluble or insoluble components of the stone particles and if there was a relationship between the differential cytokine release and generation of reactive oxygen species (ROS). Exposure of the human alveolar cell line A549 to the different particle leachates (pH 7.4 and 4.0) did not induce corresponding differential increases in the IL-8 release as observed with whole particles. Increase in ROS production, measured as dichlorofluorescein-fluorescence, was only demonstrated after exposure of A549 cells to the pH 4.0 extract from basalt. Furthermore, generation of ROS was found in neutrophils but not in A549 cells and primary macrophages after exposure to suspensions of the solid particles. However, no obvious differences in potency among the different particles were demonstrated. In summary, other mechanisms than particle-induced ROS formation seem to be responsible for the differential induction of IL-8. Furthermore, our findings indicate that the differential ability to induce IL-8 release in lung cells is attributed to the solid components of the stone particles.