title: Pulmonary response to silica or titanium dioxide: inflammatory cells, alveolar macrophage-derived cytokines, and histopathology.
abstract: We investigated the effects of silica (SiO2) and titanium dioxide (TiO2) on the pulmonary recruitment of inflammatory cells and the ability of alveolar macrophages (AMs) to release the pro-inflammatory cytokines, interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF). Rats were intratracheally instilled with 5 to 100 mg/kg of the materials, and bronchoalveolar lavage cell populations and AM cytokine release were characterized on days 1, 7, 14, and 28. Both dusts elicited dose-related increases in neutrophils, lymphocytes, and AMs; however, this response was more pronounced and persistent with SiO2. SiO2 at greater than or equal to 50 mg/kg increased AM release of IL-1 and TNF at all time points; lower SiO2 doses had either a transient or no effect on AM-derived cytokines. TiO2 did not result in AM IL-1 release and increased TNF release transiently at doses greater than or equal to 50 mg/kg. Both dusts primed AMs to release increased levels of IL-1 and TNF upon in vitro stimulation with lipopolysaccharide. Histopathology (day 28) demonstrated dose-related interstitial inflammation associated with SiO2 exposure, an effect that was less severe with TiO2. SiO2 doses of greater than or equal to 50 mg/kg elicited a granulomatous response. Development of granulomatous inflammation only at SiO2 doses for which persistent AM IL-1 release occurred suggests involvement of this cytokine in the formation of SiO2-induced granulomas. The ability of SiO2 to activate AM release of IL-1 and TNF in a more pronounced and persistent manner than TiO2 is likely responsible, at least in part, for the greater inflammation and pneumotoxicity associated with SiO2.
authors.affiliation: Human and Environmental Safety Division, Procter & Gamble Company, Cincinnati, Ohio 45239-8707.
authors.forename: K E
authors.initials: KE
authors.lastname: Driscoll
authors.forename: R C
authors.initials: RC
authors.lastname: Lindenschmidt
authors.forename: J K
authors.initials: JK
authors.lastname: Maurer
authors.forename: J M
authors.initials: JM
authors.lastname: Higgins
authors.forename: G
authors.initials: G
authors.lastname: Ridder
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D007375:Interleukin-1 / Q000096:biosynthesis*; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000473:pathology; D008214:Lymphocytes / Q000473:pathology; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000473:pathology; D011650:Pulmonary Alveoli / Q000473:pathology*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D012822:Silicon Dioxide / Q000633:toxicity*; D014025:Titanium / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C009495:titanium dioxide; D012822:Silicon Dioxide; D014025:Titanium