Satoh Minoru, Kuroda Yoshiki, Yoshida Hideo, Behney Krista M, Mizutani Akiei, Akaogi Jun, Nacionales Dina C, Lorenson Thomas D, Rosenbauer Robert J, Reeves Westley H
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.
J Autoimmun. 2003 Aug;21(1):1-9. doi: 10.1016/s0896-8411(03)00083-0.
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.
让非自身免疫小鼠接触烃类油类降植烷会诱导产生狼疮特异性自身抗体。我们研究了诱导狼疮样自身免疫的能力是降植烷独有的特性还是其他佐剂油类也具备。七组3个月大的雌性BALB/cJ小鼠分别接受一次腹腔注射降植烷、角鲨烯(用于佐剂MF59)、不完全弗氏佐剂(IFA)、三种不同的药用矿物油或生理盐水。检测血清自身抗体和腹腔细胞因子的产生情况。除了降植烷,矿物油Bayol F(IFA)和内源性烃类角鲨烯均诱导产生了抗nRNP/Sm和-Su自身抗体(分别占小鼠的20%和25%)。所有这些烃类物质对腹腔抗原呈递细胞的细胞因子产生均有持久影响。然而,腹腔注射后2至3个月时高水平的IL-6、IL-12和TNFα产生似乎与诱导狼疮自身抗体的能力有关。诱导狼疮自身抗体的能力并非降植烷所独有,几种烃类物质都具备。它与IL-12和其他细胞因子产生的刺激相关,表明与烃类物质的佐剂活性有关。诱导自身免疫的可能性可能会使油佐剂在人用和兽用疫苗中的使用变得复杂。