Kuroda Yoshiki, Nacionales Dina C, Akaogi Jun, Reeves Westley H, Satoh Minoru
Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, ARB-R2-156, 1600 SW Archer Road, P.O. Box 100221 Gainesville, FL 32610-0221, USA.
Biomed Pharmacother. 2004 Jun;58(5):325-37. doi: 10.1016/j.biopha.2004.04.009.
Adjuvant oils such as Bayol F (Incomplete Freund's adjuvant: IFA) and squalene (MF59) have been used in human and veterinary vaccines despite poor understanding of their mechanisms of action. Several reports suggest an association of vaccination and various autoimmune diseases, however, few were confirmed epidemiologically and the risk of vaccination for autoimmune diseases has been considered minimal. Microbial components, not the adjuvant components, are considered to be of primary importance for adverse effects of vaccines. We have reported that a single intraperitoneal injection of the adjuvant oils pristane, IFA or squalene induces lupus-related autoantibodies to nRNP/Sm and -Su in non-autoimmune BALB/c mice. Induction of these autoantibodies appeared to be associated with the hydrocarbon's ability to induce IL-12, IL-6, and TNF-alpha, suggesting a relationship with hydrocarbon's adjuvanticity. Whether this is relevant in human vaccination is a difficult issue due to the complex effects of vaccines and the fact that immunotoxicological effects vary depending on species, route, dose, and duration of administration. Nevertheless, the potential of adjuvant hydrocarbon oils to induce autoimmunity has implications in the use of oil adjuvants in human and veterinary vaccines as well as basic research.
尽管对佐剂油如Bayol F(不完全弗氏佐剂:IFA)和角鲨烯(MF59)的作用机制了解甚少,但它们已被用于人类和兽用疫苗中。有几份报告表明疫苗接种与各种自身免疫性疾病有关,然而,很少有报告在流行病学上得到证实,并且疫苗接种引发自身免疫性疾病的风险被认为极小。疫苗的不良反应主要被认为是由微生物成分而非佐剂成分引起的。我们曾报道,在非自身免疫性BALB/c小鼠中,单次腹腔注射佐剂油姥鲛烷、IFA或角鲨烯可诱导产生针对nRNP/Sm和-Su的狼疮相关自身抗体。这些自身抗体的诱导似乎与碳氢化合物诱导IL-12、IL-6和TNF-α的能力有关,这表明与碳氢化合物的佐剂活性存在关联。由于疫苗的复杂作用以及免疫毒理学效应因物种、途径、剂量和给药持续时间而异这一事实,这在人类疫苗接种中是否相关是一个难题。尽管如此,佐剂碳氢油诱导自身免疫的可能性对人类和兽用疫苗中油佐剂的使用以及基础研究都有影响。