Interactive effects of cerium oxide and diesel exhaust nanoparticles on inducing pulmonary fibrosis

Cerium compounds have been used as a fuel-borne catalyst to lower the generation of diesel exhaust particles (DEPs), but are emitted as cerium oxide nanoparticles (CeO₂) along with DEP in the diesel exhaust. The present study investigates the effects of the combined exposure to DEP and CeO₂ on the pulmonary system in a rat model. Specific pathogen-free male Sprague–Dawley rats were exposed to CeO₂ and/or DEP via a single intratracheal instillation and were sacrificed at various time points post-exposure. This investigation demonstrated that CeO₂ induces a sustained inflammatory response, whereas DEP elicits a switch of the pulmonary immune response from Th1 to Th2. Both CeO₂ and DEP activated AM and lymphocyte secretion of the proinflammatory cytokines IL-12 and IFN-γ, respectively. However, only DEP enhanced the anti-inflammatory cytokine IL-10 production in response to ex vivo LPS or Concanavalin A challenge that was not affected by the presence of CeO₂, suggesting that DEP suppresses host defense capability by inducing the Th2 immunity. The micrographs of lymph nodes show that the particle clumps in DEP + CeO₂ were significantly larger than CeO₂ or DEP, exhibiting dense clumps continuous throughout the lymph nodes. Morphometric analysis demonstrates that the localization of collagen in the lung tissue after DEP + CeO₂ reflects the combination of DEP-exposure plus CeO₂-exposure. At 4 weeks post-exposure, the histological features demonstrated that CeO₂ induced lung phospholipidosis and fibrosis. DEP induced lung granulomas that were not significantly affected by the presence of CeO₂ in the combined exposure. Using CeO₂ as diesel fuel catalyst may cause health concerns.