Induction of lupus-related specific autoantibodies by non-specific inflammation caused by an intraperitoneal injection of n-hexadecane in BALB/c mice.

Abstract

A single intraperitoneal (i.p.) injection of pristane, incomplete Freund's adjuvant (IFA), or the adjuvant oil squalene, but not high molecular weight medicinal mineral oils, induces lupus-related autoantibodies to nRNP/Sm and -Su in non-autoimmune strains of mice. This ability appears to be associated with the low molecular weight and adjuvanticity of hydrocarbon. n-Hexadecane (C(16)H(34)), which is present in petroleum, has adjuvant activity and induces arthritis in rodents like other lupus-inducing oils. In addition to dietary exposure to n-hexadecane in mineral oils, exposure also occurs via inhalation of oil mist, jet fuel, or diesel exhaust or by absorption through the skin. Since n-hexadecane is a low molecular weight adjuvant hydrocarbon oil similar to other lupus-inducing hydrocarbons, the present study examined whether it can also induce lupus-related autoantibodies in mice. Female BALB/cJ mice received a single i.p. injection of 0.5 ml of n-hexadecane, pristane, or saline (control). Pathology and serology (immunoglobulin levels, autoantibodies by immunofluorescence, immunoprecipitation, and ELISA) were examined 3 months later. Unexpectedly, all n-hexadecane-treated mice, but none in the other groups, developed inflammatory ascites within 2.5 months. n-Hexadecane induced hypergammaglobulinemia (IgG1, IgG2a), antinuclear (titer>1:160, 67%) and -cytoplasmic antibodies (58%) and autoantibodies to nRNP/Sm (25%), Su (33%), ssDNA (83%), and chromatin (100%). Therefore, non-specific inflammation caused by n-hexadecane resulted in the production of a limited set of specific autoantibodies. These previously unrecognized immunological effects of n-hexadecane may have implications in monitoring human exposure to hydrocarbons and in the pathogenesis of autoimmune diseases.

• Authors: Yoshiki Kuroda, Nobutaka Ono, Jun Akaogi, Dina C Nacionales, Yoshioki Yamasaki, Tolga T Barker, Westley H Reeves, Minoru Satoh
• Journal: Toxicology (Toxicology) Vol. 218 Issue 2-3 Pg. 186-96 (Feb 01 2006) ISSN: 0300-483X [Print] Ireland
• PMID: 16309812 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Alkanes
• Autoantibodies
• Environmental Pollutants
• n-hexadecane

Topics

• Alkanes (toxicity)
• Animals
• Ascites (chemically induced)
• Autoantibodies (immunology)
• Autoimmunity
• Environmental Pollutants (toxicity)
• Female
• Injections, Intraperitoneal
• Liver (drug effects, pathology)
• Lupus Vulgaris (chemically induced, immunology)
• Mice
• Mice, Inbred BALB C
• Peritonitis (chemically induced)
• Spleen (drug effects, pathology)