PULMONARY INFLAMMATORY RESPONSES AND CYTOKINE AND ANTIOXIDANT mRNA LEVELS IN THE LUNGS OF YOUNG AND OLD C57BL/6 MICE AFTER EXPOSURE TO TEFLON FUMES

Abstract

Our past studies in rats have confirmed the high pulmonary toxicity of inhaled Teflon fumes containing ultrafine particles. These previous studies had been performed in young adult animals. We hypothesized that older animals would be more susceptible to induction of an inflammatory response. The purpose of our study was to characterize the acute pulmonary inflammatory response in the lungs of healthy C57BL/6 adult mice of 8wk and 18 mo of age after short-term (30 min) exposure to low concentrations (<50 mug/m3) of singlet ultrafine PTFE fume particles. Mice were exposed to air, 1 x 105, 2.5 x 105, or 5 x 105 particles/cm3 for 30 min and sacrificed 6 h postexposure. Median particle size was ~20 nm. Lung lavage and total RNA isolation of the lung were performed. Message levels for the interleukins IL-1, IL-1, IL-2, IL-3, IL-4, IL-5, and IL-6, for interferon (IFN), for tumor necrosis factor (TNF) and TNF, for Mn superoxide dismutase (SOD), and for metallothionein (Mt) were measured. Compared to the previous studies in rats with the same exposure concentrations, the inflammatory response elicited in mice was less severe and no deaths occurred. The lowest exposure concentration had no effect on message levels in either group of mice. The mid-exposure level increased mRNA levels for messages encoding IL-1, IL-3, IL-6, MnSOD, and Mt in young C57BL/6 mice. In contrast, at this level less dramatic increases were measured for IL-1, IL-6, and Mt in old mice. After the highest exposure concentration, IL-1, IL-3, IL-6, Mt, and MnSOD were increased to levels similar to those measured after a 2.5 x 105particles/cm3 exposure in young mice. Old mice also demonstrated increased mRNA abundance for IL-1, IL-3, IL-6, Mt, and MnSOD after a 5 x 105 particles/cm3 exposure. However, at this concentration TNF mRNA levels were induced 12-fold in old mice, whereas only a threefold induction was measured in 8-wk-old mice. Lung lavage PMN levels were also threefold greater in the old mice compared to young mice. These findings suggest inflammatory response to PTFE fumes with ultrafine particles is altered with age, and that the inflammatory response is greater in the old animals.