Toxic oil syndrome: Genetic restriction and immunomodulatory effects due to adulterated oils in a model of HLA transgenic mice

• Published in: Toxicology letters Vol. 159; no. 2; pp. 173 - 181
• Main Authors: Gallardo, Soledad, Cárdaba, Blanca, Posada, Manuel, del Pozo, Victoria, Messeguer, Angel, David, Chella S., Lahoz, Carlos
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 15.11.2005; Amsterdam Elsevier Science
• Subjects: Aniline Compounds - toxicity; Animals; Biological and medical sciences; Canola Oil; Eosinophilia; Eosinophils - drug effects; Eosinophils - immunology; Fatty Acids, Monounsaturated; Female; Genetic Predisposition to Disease; Histocompatibility Antigens Class II - genetics; HLA; Humans; Immunoglobulin E - blood; Interleukin-4 - biosynthesis; Interleukin-5 - biosynthesis; Lung - drug effects; Lung - immunology; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Transgenic; Plant Oils - toxicity; Propylene Glycols - toxicity; RNA, Messenger - biosynthesis; Syndrome; Th2 Cells - drug effects; Th2 Cells - immunology; Th2 pattern; Toxic oil syndrome; Toxicology; Toxiepidemic; Transgenic mice; Th2 pattern; Toxic oil syndrome; Toxiepidemic; HLA; Eosinophilia; Transgenic mice; HLA-System; Immunomodulation; Major histocompatibility system; Rodentia; Transgenic animal; Hemopathy; Syndrome; Immunomodulator; Vertebrata; Mammalia; Oil; HLA-A-Locus; Mouse; T-Lymphocyte; Genetics; Th2 lymphocyte; Models; Class I histocompatibility antigen
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2005.05.009

Toxic oil syndrome (TOS) was described in Spain in 1981, due to the ingestion of contaminated rapeseed oil denatured with 2% aniline. More than 20,000 persons were affected, causing over 2500 deaths. Immunological findings were: eosinophilia, mRNA for Th2 cytokines (IL-4 and IL-5) in lungs, elevated total IgE and sIL-2R and increase of DR2 HLA class II phenotypic frequency in patients died by TOS. Our objective is to test the genetic restriction found in humans using HLA transgenic mice. Results show that mice expressing human DR2 and DQ6 (both in linkage disequilibrium), had higher percentage of eosinophils (DQ6) and IgE (DR2) than other transgenic mice tested (DR3 and DR4). Also, a Th2 shift was found in DR2 transgenic mice when toxic oil was administered with OVA. This has been corroborated by the IL-5 mRNA expression in 4 out of 6 lung tissues from TOS oil treated BALB/c mice. These data indicate that an immunological response was induced as consequence of the toxic administration. These results correlate with those found in TOS patients and reinforce the implication of genetic restrictions in the acquisition of toxic-mediated disease.