ToxSci Advance Access originally published online on January 12, 2004
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Toxicological Sciences 78, 222-228 (2004)
Toxicological Sciences vol. 78 no. 2 © Society of Toxicology; all rights reserved.
Distinctive Patterns of Autoimmune Response Induced by Different Types of Mineral Oil
,1
* Division of Rheumatology and Clinical Immunology, Department of Medicine, Analytical Toxicology Core Laboratory, Department of Physiological Sciences, and Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, Florida 32610-0221
Received October 9, 2003; accepted December 19, 2003
Although mineral oils are generally considered nontoxic 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 nonautoimmune 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. Female 3-month-old BALB/c (16–45/group) mice each received an i.p. injection of pristane (C19), squalene (C30), IFA, three 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 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 versus –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 nontoxic also may have pathogenetic implications in human autoimmune diseases.
Key Words: mineral oil; pristane; autoimmunity; autoantibodies; antinuclear antibodies; lupus.
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