title: Pristane-induced autoimmunity in germ-free mice.
abstract: Hypergammaglobulinemia and autoantibodies are reduced in pristane-treated specific pathogen-free mice vs. conventionally housed controls, consistent with the role of microbial stimulation in this model. To determine whether microbial stimulation is required, BALB/c mice housed under germ-free conditions were treated i.p. with sterile PBS or pristane and examined 6 months later. As in conventional mice, pristane-treated germ-free mice developed peritoneal granulomas and hypergammaglobulinemia with increased IgG2a/IgG1 ratios. LPS stimulation induced more IL-6, IL-12, and TNF-alpha, and anti-CD3 induced more IFN-gamma and IL-4 by peritoneal cells from pristane-treated mice vs. control. Anti-nRNP/Sm and -Su autoantibodies were found in 40% and 43%, respectively, of pristane-treated germ-free mice by immunoprecipitation. Thus, bacterial stimulation was not required for lupus autoantibodies, peritoneal granuloma formation, hypergammaglobulinemia, or cytokine overproduction. Although microbial stimulation acts synergistically with pristane, these results clearly indicate that pristane does not act merely by increasing exposure to microbial products such as LPS.
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, Gainesville, FL 32610-0221, USA.
authors.forename: Akiei
authors.initials: A
authors.lastname: Mizutani
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Shaheen
authors.forename: Hideo
authors.initials: H
authors.lastname: Yoshida
authors.forename: Jun
authors.initials: J
authors.lastname: Akaogi
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kuroda
authors.forename: Dina C
authors.initials: DC
authors.lastname: Nacionales
authors.forename: Yoshioki
authors.initials: Y
authors.lastname: Yamasaki
authors.forename: Michito
authors.initials: M
authors.lastname: Hirakata
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Ono
authors.forename: Westley H
authors.initials: WH
authors.lastname: Reeves
authors.forename: Minoru
authors.initials: M
authors.lastname: Satoh
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001835:Body Weight; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006099:Granuloma / Q000276:immunology; D006651:Histocytochemistry; D006942:Hypergammaglobulinemia / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology / Q000473:pathology; D018709:Statistics, Nonparametric; D013729:Terpenes / Q000276:immunology / Q000494:pharmacology*
chemical_list: D001323:Autoantibodies; D016207:Cytokines; D013729:Terpenes; C009042:pristane