The soluble metal fraction of residual oil fly ash (ROFA) has been shown to increase the susceptibility to infection in animal models. The goal of this study was to determine which of the primary soluble metals or metal combinations in ROFA were responsible for the increased infectivity. The soluble fraction of ROFA contained Ni, Fe, Al, and Zn. On Day 0, Sprague-Dawley rats were intratracheally (IT) instilled with NiCl2 (55.7 µg/rat), FeSO4 (32.7 µg/rat), Al3(SO4)2 (46.6 µg/rat), or ZnCl2 (8.69 µg/rat), or a combination of all the metals (Total Mixture). In a separate experiment, rats were instilled with metal mixtures, including the total mixture, and mixtures without Fe (Mix - No Fe), Ni (Mix - No Ni), Al (Mix - No Al), or Zn (Mix - No Zn). At Day 3, rats were instilled with 5 × 104 Listeria monocytogenes. At Days 6, 8 and 10, left lungs were removed to assess bacterial clearance. Bronchoalveolar lavage (BAL) was performed on right lungs on Day 3, before infection, and on Days 6, 8 and 10 to assess lung injury and cellular activity. Prior to infection, soluble Ni and mixtures containing Ni significantly increased lung injury, inflammation, and oxidative damage to a comparable degree when compared to control. Post-infection, rats pre-treated with soluble Ni, alone or in a metal mixture, had increased bacterial lung burden on Day 6, and body weight decreased in the soluble Ni, Mix - No Fe, and Mix - No Al groups post-infection, indicating Fe and Al may act antagonistically to Ni. Ni alone and in metal mixtures increased reactive oxidants in the lung and appeared to be the most important factor in suppressing T-cell activity post-infection. Soluble Ni is likely the primary metal involved in the increased susceptibility to infection observed in rats exposed to the soluble metals of ROFA.
Animals; Animal-studies; Bacterial-disease; Bacterial-infections; Biodynamics; Biohazards; Biological-effects; Breathing; Cell-function; Cell-metabolism; Cellular-function; Diseases; Infectious-diseases; Infection-control; Immune-system-disorders; Infection-control; Immunologic-disorders; Immunotoxins; Lung-cells; Lung-irritants; Laboratory-animals; Metal-dusts; Metallic-compounds; Metallic-dusts; Metallic-poisons; Metals; Oxidation; Oxidative-processes; Pulmonary-disorders; Pulmonary-system-disorders; Risk-factors; Risk-analysis; Statistical-analysis;
Author Keywords: lung; Listeria monocytogenes; immunotoxicology; fly ash; nickle compounds
Jenny R. Roberts, Ph.D., Health Effects Laboratory Division, National Institute for Occupational Safety and Health (NIOSH), 1095 Willowdale Drive (M/S 2015), Morgantown, WV 26505