title: Induction of lupus autoantibodies by adjuvants.
abstract: Exposure to the hydrocarbon oil pristane induces lupus specific autoantibodies in non-autoimmune mice. We investigated whether the capacity to induce lupus-like autoimmunity is a unique property of pristane or is shared by other adjuvant oils. Seven groups of 3-month-old female BALB/cJ mice received a single intraperitoneal injection of pristane, squalene (used in the adjuvant MF59), incomplete Freund's adjuvant (IFA), three different medicinal mineral oils, or saline, respectively. Serum autoantibodies and peritoneal cytokine production were measured. In addition to pristane, the mineral oil Bayol F (IFA) and the endogenous hydrocarbon squalene both induced anti-nRNP/Sm and -Su autoantibodies (20% and 25% of mice, respectively). All of these hydrocarbons had prolonged effects on cytokine production by peritoneal APCs. However, high levels of IL-6, IL-12, and TNFalpha production 2-3 months after intraperitoneal injection appeared to be associated with the ability to induce lupus autoantibodies. The ability to induce lupus autoantibodies is shared by several hydrocarbons and is not unique to pristane. It correlates with stimulation of the production of IL-12 and other cytokines, suggesting a relationship with a hydrocarbon's adjuvanticity. The potential to induce autoimmunity may complicate the use of oil adjuvants in human and veterinary vaccines.
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, P.O. Box 100221, 1600 SW Archer Road, Gainesville, FL 32610-0221, USA. satohm@medicine.ufl.edu
authors.forename: Minoru
authors.initials: M
authors.lastname: Satoh
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kuroda
authors.forename: Hideo
authors.initials: H
authors.lastname: Yoshida
authors.forename: Krista M
authors.initials: KM
authors.lastname: Behney
authors.forename: Akiei
authors.initials: A
authors.lastname: Mizutani
authors.forename: Jun
authors.initials: J
authors.lastname: Akaogi
authors.forename: Dina C
authors.initials: DC
authors.lastname: Nacionales
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Lorenson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Rosenbauer
authors.forename: Westley H
authors.initials: WH
authors.lastname: Reeves
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D001323:Autoantibodies / Q000187:drug effects* / Q000276:immunology*; D001324:Autoantigens; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005620:Freund's Adjuvant / Q000009:adverse effects; D007074:Immunoglobulin G / Q000097:blood / Q000187:drug effects; D018664:Interleukin-12 / Q000378:metabolism; D008055:Lipids / Q000009:adverse effects; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010537:Peritoneum / Q000187:drug effects / Q000378:metabolism; D011506:Proteins / Q000276:immunology; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology; D013185:Squalene / Q000009:adverse effects; D013729:Terpenes / Q000494:pharmacology; D055517:snRNP Core Proteins
chemical_list: D000276:Adjuvants, Immunologic; D001323:Autoantibodies; D001324:Autoantigens; D016207:Cytokines; D007074:Immunoglobulin G; D008055:Lipids; D011506:Proteins; D017411:Ribonucleoproteins, Small Nuclear; C089635:Su autoantigen; D013729:Terpenes; C114843:incomplete Freund's adjuvant; D055517:snRNP Core Proteins; D018664:Interleukin-12; C009042:pristane; D013185:Squalene; D005620:Freund's Adjuvant