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 wid ely in potency to induce inflammatory cytokines (IL-6, IL-8 and TNF-alpha) in different types of lung cells. In this study we investigated if the obse rved cytokine responses were associated with the soluble or insoluble compo nents of the stone particles and if there was a relationship between the di fferential cytokine release and generation of reactive oxygen species (ROS) . Exposure of the human alveolar cell line A549 to the different particle l eachates (pH 7.4 and 4.0) did not induce corresponding differential increas es in the IL-8 release as observed with whole particles. Increase in ROS pr oduction, measured as dichlorofluorescein-fluorescence, was only demonstrat ed after exposure of A549 cells to the pH 4.0 extract from basalt. Furtherm ore, generation of ROS was found in neutrophils but not in A549 cells and p rimary macrophages after exposure to suspensions of the solid particles. Ho wever, no obvious differences in potency among the different particles were demonstrated. In summary, other mechanisms than particle-induced ROS forma tion seem to be responsible for the differential induction of IL-8. Further more, our findings indicate that the differential ability to induce IL-8 re lease in lung cells is attributed to the solid components of the stone part icles. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.