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ToxSci Advance Access published online on January 12, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh063
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
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Received October 9, 2003; accepted December 19, 2003
© 2004 Society of Toxicology

Immunotoxicology

Distinctive Patterns of Autoimmune Response Induced by Different Types of Mineral Oil

Yoshiki Kuroda 1, Jun Akaogi 1, Dina C. Nacionales 1, Scott C. Wasdo 2, Nancy J. Szabo 2, Westley H. Reeves 3, and Minoru Satoh 3*

1 Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, Gainesville, FL 32610-0221, USA
2 Analytical Toxicology Core Laboratory, Department of Physiological Sciences, University of Florida, Gainesville, FL 32610-0221, USA
3 Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, Gainesville, FL 32610-0221, USA; Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32610-0221 USA

* To whom correspondence should be addressed. E-mail: satohm{at}medicine.ufl.edu.


  Abstract

Although mineral oils are generally considered non-toxic 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 non-autoimmune 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. Three-month old female BALB/c (16-45/group) mice received an i.p. injection of pristane (C19), squalene (C30), IFA, 3 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 of 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 vs. -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 non-toxic also may have pathogenetic implications in human autoimmune diseases.

Key Words: mineral oil, pristane, autoimmunity, autoantibodies, antinuclear antibodies, lupus .


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