title: Distinctive patterns of autoimmune response induced by different types of mineral oil.
abstract: Although mineral oils are generally considered nontoxic and have a long history of use in humans, the mineral oil Bayol F (incomplete Freund's adjuvant, IFA) and certain mineral oil components (squalene and n-hexadecane) induce lupus-related anti-nRNP/Sm or -Su autoantibodies in nonautoimmune mice. In the present study, we investigated whether medicinal mineral oils can induce other types of autoantibodies and whether structural features of hydrocarbons influence autoantibody specificity. Female 3-month-old BALB/c (16-45/group) mice each received an i.p. injection of pristane (C19), squalene (C30), IFA, three medicinal mineral oils (MO-F, MO-HT, MO-S), or PBS. Sera were tested for autoantibodies and immunoglobulin levels. Hydrocarbons were analyzed by gas chromatography/mass spectrometry. IFA contained mainly C15-C25 hydrocarbons, whereas MO-HT and MO-S contained C20-C40, and MO-F contained C15-C40. Pristane and n-hexadecane were found in IFA (0.17% and 0.10% w/v, respectively) and MOs (0.0026-0.027%). At 3 months, pristane and IFA induced mainly IgG2a, squalene IgG1, and MOs IgG3 and IgM in sera. Anti-cytoplasmic antibodies were common in mice treated with MO-F, as well as those treated with pristane, squalene, and IFA. Anti-ssDNA and -chromatin antibodies were higher in MO-F and MO-S than in untreated/PBS, squalene-, or IFA-treated mice, suggesting that there is variability in the induction of anti-nRNP/Sm versus -chromatin/DNA antibodies. The preferential induction of anti-chromatin/ssDNA antibodies without anti-nRNP/Sm/Su by MO-S and MO-F is consistent with the idea that different types of autoantibodies are regulated differently. Induction of autoantibodies by mineral oils considered nontoxic also may have pathogenetic implications in human autoimmune diseases.
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, Gainesville, Florida 32610-0221, USA.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kuroda
authors.forename: Jun
authors.initials: J
authors.lastname: Akaogi
authors.forename: Dina C
authors.initials: DC
authors.lastname: Nacionales
authors.forename: Scott C
authors.initials: SC
authors.lastname: Wasdo
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Szabo
authors.forename: Westley H
authors.initials: WH
authors.lastname: Reeves
authors.forename: Minoru
authors.initials: M
authors.lastname: Satoh
mesh_terms: D000473:Alkanes / Q000032:analysis; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis / Q000097:blood; D001323:Autoantibodies / Q000096:biosynthesis* / Q000097:blood; D015551:Autoimmunity; D002843:Chromatin / Q000276:immunology; D004277:DNA, Single-Stranded / Q000276:immunology; D005260:Female; D005620:Freund's Adjuvant / Q000737:chemistry / Q000633:toxicity; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006942:Hypergammaglobulinemia / Q000097:blood / Q000139:chemically induced*; D007136:Immunoglobulins / Q000096:biosynthesis / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008899:Mineral Oil / Q000737:chemistry / Q000633:toxicity*; D013185:Squalene / Q000032:analysis / Q000633:toxicity; D013729:Terpenes / Q000032:analysis / Q000633:toxicity
chemical_list: D000473:Alkanes; D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D002843:Chromatin; D004277:DNA, Single-Stranded; D007136:Immunoglobulins; D013729:Terpenes; C009042:pristane; D013185:Squalene; D008899:Mineral Oil; D005620:Freund's Adjuvant; C007932:n-hexadecane