title: Induction of lupus-related specific autoantibodies by non-specific inflammation caused by an intraperitoneal injection of n-hexadecane in BALB/c mice.
abstract: A single intraperitoneal (i.p.) injection of pristane, incomplete Freund's adjuvant (IFA), or the adjuvant oil squalene, but not high molecular weight medicinal mineral oils, induces lupus-related autoantibodies to nRNP/Sm and -Su in non-autoimmune strains of mice. This ability appears to be associated with the low molecular weight and adjuvanticity of hydrocarbon. n-Hexadecane (C(16)H(34)), which is present in petroleum, has adjuvant activity and induces arthritis in rodents like other lupus-inducing oils. In addition to dietary exposure to n-hexadecane in mineral oils, exposure also occurs via inhalation of oil mist, jet fuel, or diesel exhaust or by absorption through the skin. Since n-hexadecane is a low molecular weight adjuvant hydrocarbon oil similar to other lupus-inducing hydrocarbons, the present study examined whether it can also induce lupus-related autoantibodies in mice. Female BALB/cJ mice received a single i.p. injection of 0.5 ml of n-hexadecane, pristane, or saline (control). Pathology and serology (immunoglobulin levels, autoantibodies by immunofluorescence, immunoprecipitation, and ELISA) were examined 3 months later. Unexpectedly, all n-hexadecane-treated mice, but none in the other groups, developed inflammatory ascites within 2.5 months. n-Hexadecane induced hypergammaglobulinemia (IgG1, IgG2a), antinuclear (titer>1:160, 67%) and -cytoplasmic antibodies (58%) and autoantibodies to nRNP/Sm (25%), Su (33%), ssDNA (83%), and chromatin (100%). Therefore, non-specific inflammation caused by n-hexadecane resulted in the production of a limited set of specific autoantibodies. These previously unrecognized immunological effects of n-hexadecane may have implications in monitoring human exposure to hydrocarbons and in the pathogenesis of autoimmune diseases.
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, ARB-R2-156, 1600 SW Archer Road, Box 100221, Gainesville, FL 32610-0221, USA.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kuroda
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Ono
authors.forename: Jun
authors.initials: J
authors.lastname: Akaogi
authors.forename: Dina C
authors.initials: DC
authors.lastname: Nacionales
authors.forename: Yoshioki
authors.initials: Y
authors.lastname: Yamasaki
authors.forename: Tolga T
authors.initials: TT
authors.lastname: Barker
authors.forename: Westley H
authors.initials: WH
authors.lastname: Reeves
authors.forename: Minoru
authors.initials: M
authors.lastname: Satoh
mesh_terms: D000473:Alkanes / Q000633:toxicity*; D000818:Animals; D001201:Ascites / Q000139:chemically induced; D001323:Autoantibodies / Q000276:immunology*; D015551:Autoimmunity; D004785:Environmental Pollutants / Q000633:toxicity; D005260:Female; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008177:Lupus Vulgaris / Q000139:chemically induced* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010538:Peritonitis / Q000139:chemically induced; D013154:Spleen / Q000187:drug effects / Q000473:pathology
chemical_list: D000473:Alkanes; D001323:Autoantibodies; D004785:Environmental Pollutants; C007932:n-hexadecane