Characterization of the Early Pulmonary Inflammatory Response Associated with PTFE Fume Exposure

Abstract

Heating of polytetrafluoroethylene (PTFE) has been described to release fumes containing ultrafine particles (∼18 nm diam). These fumes can be highly toxic in the respiratory tract inducing extensive pulmonary edema with hemorrhagic inflammation. Fischer-344 rats were exposed to PTFE fumes generated by temperatures ranging from 450 to 460°C for 15 min at an exposure concentration of 5 × 105particles/cm3, equivalent to ∼50 μg/m3. Responses were examined 4 hr post-treatment when these rats demonstrated 60–85% neutrophils (PMNs) in their lung lavage. Increases in abundance for messages encoding the antioxidants manganese superoxide dismutase and metallothionein (MT) increased 15- and 40-fold, respectively. For messages encoding the pro- and anti-inflammatory cytokines: inducible nitric oxide synthase, interleukin 1α, 1β, and 6 (IL-1α, IL-1β, and IL-6), macrophage inflammatory protein-2, and tumor necrosis factor-α (TNFα) increases of 5-, 5-, 10-, 40-, 40-, and 15-fold were present. Vascular endothelial growth factor, which may play a role in the integrity of the endothelial barrier, was decreased to 20% of controls.In situsections were hybridized with33P cRNA probes encoding IL-6, MT, surfactant protein C, and TNFα. Increased mRNA abundance for MT and IL-6 was expressed around all airways and interstitial regions with MT and IL-6 demonstrating similar spatial distribution. Large numbers of activated PMNs expressed IL-6, MT, and TNFα. Additionally, pulmonary macrophages and epithelial cells were actively involved. These observations support the notion that PTFE fumes containing ultrafine particles initiate a severe inflammatory response at low inhaled particle mass concentrations, which is suggestive of an oxidative injury. Furthermore, PMNs may actively regulate the inflammatory process through cytokine and antioxidant expression.