Review Article Toxic Oil Syndrome: Review of Immune Aspects of the Disease

Abstract

In 1981-1982, individuals in fourteen central and northwest provinces in Spain were affected by an illness that was eventually labeled toxic oil syndrome (TOS) by the World Health Organization. Thousands of individuals were diagnosed with, and 356 people eventually died from, the disease. The disease shares striking similarities with several autoimmune diseases, particularly eosinophilia-myalgia syndrome (EMS) and diffuse fasciitis with eosinophilia (DFE). As with many other autoimmune diseases, women were more severely affected than men and made up a significant portion of TOS-related deaths. While a number of etiologic agents were investigated, disease occurrence was found to be significantly associated with consumption of contaminated rapeseed oil produced by a particular refinery. Two compounds, 1,2-di-oleyl ester (DEPAP) and oleic anilide are considered to be biologically relevant contaminants that may contribute to disease development. Toxic oil syndrome was a three-phase disease with an initial non-necrotizing vasculitis in multiple organs. Suspected immune mechanisms in TOS include activation of T-cells, altered cytokine production, and several studies have associated disease severity with HLA-DR2 and polymorphisms in metabolism and immune response genes. While a number of animal models have been used to investigate the underlying immune mechanisms in TOS, only a few studies in rodents have demonstrated the classical symptoms of TOS. Biotransformation and oxidation of the parent compound(s) to reactive intermediates prior to induction of autoreactive pathways appears to be an important component of the disease process. These reactive intermediates could haptenate self-proteins and activate autoreactive T-cells, disrupt signal transduction, or induce apoptosis and necrosis to release abnormal forms of self-antigens. Although the TOS epidemic was limited to a discrete period of time, the origin of the contamination determined, and the spread of the disease halted by government intervention, the underlying immune mechanisms have yet to be elucidated.

Toxic Myopathies

“…The toxic oil syndrome was quite similar to the eosinophilia-myalgia syndrome associated with tryptophan (75). This condition was restricted to a single epidemic in spain and has not recurred since 1981-1982.…”

Eosinophilia-myalgia syndrome induced by excessive L-tryptophan intake from cashew nuts

“…On this theory an alternative explanation for the 1989 EMS outbreak was based; that excess histamine caused EMS. Since not all consumers who used implicated drug in 1989 developed EMS, genetic and other factors are also likely to play a role in precipitation of EMS [9].…”

Untitled

“…toxic oil syndrome (Gelpí et al, 2002;Patterson and Germolec, 2005), and was not covered in the SCF criteria, and endorses its inclusion.…”