title: Suppression in lung defense responses after bacterial infection in rats pretreated with different welding fumes.
abstract: Epidemiology suggests that inhalation of welding fumes increases the susceptibility to lung infection. The effects of chemically distinct welding fumes on lung defense responses after bacterial infection were compared. Fume was collected during gas metal arc (GMA) or flux-covered manual metal arc (MMA) welding using two consumable electrodes: stainless steel (SS) or mild steel (MS). The fumes were separated into water-soluble and -insoluble fractions. The GMA-SS and GMA-MS fumes were found to be relatively insoluble, whereas the MMA-SS was highly water soluble, with the soluble fraction comprised of 87% Cr and 11% Mn. On day 0, male Sprague-Dawley rats were intratracheally instilled with saline (vehicle control) or the different welding fumes (0.1 or 2 mg/rat). At day 3, the rats were intratracheally inoculated with 5 x 10(3) Listeria monocytogenes. On days 6, 8, and 10, left lungs were removed, homogenized, cultured overnight, and colony-forming units were counted to assess pulmonary bacterial clearance. Bronchoalveolar lavage (BAL) was performed on right lungs to recover phagocytes and BAL fluid to measure the production of nitric oxide (NO) and immunomodulatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-2, IL-6, and IL-10. In contrast to the GMA-SS, GMA-MS, and saline groups, pretreatment with the highly water soluble MMA-SS fume caused significant body weight loss, extensive lung damage, and a dramatic reduction in pulmonary clearance of L. monocytogenes after infection. NO concentrations in BAL fluid and lung immunostaining of inducible NO synthase were dramatically increased in rats pretreated with MMA-SS before and after infection. MMA-SS treatment caused a significant decrease in IL-2 and significant increases in TNF-alpha, IL-6, and IL-10 after infection. In conclusion, pretreatment with MMA-SS increased production of NO and proinflammatory cytokines (TNF-alpha and IL-6) after infection, which are likely responsible for the elevation in lung inflammation and injury. In addition, MMA-SS treatment reduced IL-2 (involved in T cell proliferation) and enhanced IL-10 (involved in inhibiting macrophage function) after bacterial infection, which might result in a possible suppression in immune response and an increase in susceptibility to infection.
authors.affiliation: Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA. jga6@cdc.gov
authors.forename: James M
authors.initials: JM
authors.lastname: Antonini
authors.forename: Michael D
authors.initials: MD
authors.lastname: Taylor
authors.forename: Lyndell
authors.initials: L
authors.lastname: Millecchia
authors.forename: Alicia R
authors.initials: AR
authors.lastname: Bebout
authors.forename: Jenny R
authors.initials: JR
authors.lastname: Roberts
mesh_terms: D000395:Air Pollutants, Occupational / Q000032:analysis / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008088:Listeriosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008163:Luminescent Measurements; D008171:Lung Diseases / Q000276:immunology* / Q000473:pathology; D008297:Male; D008670:Metals / Q000032:analysis / Q000633:toxicity; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013193:Stainless Steel / Q000633:toxicity; D014132:Trachea / Q000276:immunology / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis; D014896:Welding
chemical_list: D000395:Air Pollutants, Occupational; D016207:Cytokines; D015850:Interleukin-6; D008670:Metals; D014409:Tumor Necrosis Factor-alpha; D013193:Stainless Steel; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase