Strain-Dependent Cytokine Profile and Susceptibility to Oleic Acid Anilide in a Murine Model of the Toxic Oil Syndrome

Berking, Carola; Hobbs, Monte V.; Châtelain, R; Meurer, Michael; Bell, Susanne A.

doi:10.1006/taap.1997.8327

Cited by 23 publications

(22 citation statements)

References 27 publications

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“…Although the compounds responsible for the toxicity have not been de nitively identi ed, there is a strong association between risk of the diseases and 2 different families of compounds found in the oils which came from case families. When the outbreak started, the oleyl anilides were associated with the diseases (5,18,28), but a more detailed analysis of those oils showed that the fatty acid esters 3(N-phenylamino)-1,2-propanediol (PAP) (4,7,11,14,29,30) were the best predictors of the case oil. To reconstruct the pathogenesis of this disease, identify the toxic principal(s) responsible for the disease, and to determine the role of the immune system in disease induction and/or progression, development of an animal model representative of the disease in humans would contribute basic information to this process.…”

Section: Introductionmentioning

confidence: 99%

Pathology of “Toxic Oils” and Selected Metals in the MRL/lpr Mouse

et al. 2001

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The Toxic Oil Syndrome epidemic that occurred in Spain in 1981 and affected nearly 20,000 people was caused by ingestion of oil mixtures that contained analine-denatured rapeseed oil. To date, an animal model in which to identify the actual etiologic agents(s) and to investigate the pathogenesi s of the disease has not been discovered . In this study, the MRL/lpr was used to assess the histopathologica l response of 3 "toxic oils" and 3 metals. The oils tested were a denatured rapeseed oil collected from a family who were affected by the Toxic Oil Syndrome epidemic in Spain (CO756) plus two synthesized oils (RSD and RSA). Female mice, 7 weeks of age, received an undiluted (neat) or a 1:10 diluted dose of each oil; mercury (50 ppm), cadmium (100 ppm), or lead (50 ppm). Half of each group was killed after 5 weeks of exposure and the remaining mice after 10 weeks of exposure. Body and organ weights (liver, kidney, thymus, and spleen) were recorded and selected organs were collected for histopathology. Ten weeks after treatment, body weights (BW) of the cadmium and lead groups were signi cantly suppressed , and the body weight of the CO756-neat group was signi cantly increased compared to their respective controls. Kidney/BW were decreased in the RSA-neat and RSA 1:10 groups after 10 weeks of exposure, and the kidney/BW in the mercury and cadmium groups were increased. Spontaneous developmen t (12 weeks of age) and progression (17 weeks of age) of histopathologica l lesions are described for selected organs examined in the naṏ ve mice as are changes that resulted from exposure to the "toxic oils" and metals. CO756-neat, mercury, and lead suppressed progression of the glomerulonephriti s that normally occurs in the MRL/lpr mouse. Also of interest were lesions that included mononuclea r cuf ng of hepatic bile ducts, progression of the granulomas that formed in the renal glomeruli, vessels in the lymphoid organs that contained tightly packed lymphocytes , and the presence of plasma cells in the thymus. All 3 oils stimulated early developmen t of the lymphoproliferative syndrome characteristic of the MRL/lpr mouse as demonstrated by an increase in the thymus/BW and spleen/BW ratios after 5 weeks of treatment. These data contribute to our knowledge of spontaneou s disease progression in the thymus, spleen, lymph nodes, and kidneys in the MRL/lpr mouse and the effects of 3 different "toxic oils" and metals on the developmen t and progression of those lesions.

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Section: Introductionmentioning

confidence: 99%

Pathology of “Toxic Oils” and Selected Metals in the MRL/lpr Mouse

et al. 2001

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“…Experiments with different strains of inbred mice clearly reflect the importance of genetics. For example, whereas C57 BL/6 (H-2b) mice are symptom-free following oral challenge with oleic acid anilide, a severe rapid wasting disease is seen in similarly challenged A/J (H-2a) mice (5). In addition, however, some data suggest that the incidence of autoimmune disease may be increasing and that differences in various ethnic and geographic populations might be reflective, not only of genetic, but also of environmental influences.…”

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confidence: 99%

Evidence for the role of environmental agents in the initiation or progression of autoimmune conditions.

Powell

Water

Gershwin

1999

Environ Health Perspect

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The concordance of autoimmune disease among identical twins is virtually always less than 50% and often in the 25-40% range. This observation, as well as epidemic clustering of some autoimmune diseases following xenobiotic exposure, reinforces the thesis that autoimmune disease is secondary to both genetic and environmental factors. Because nonliving agents do not have genomes, disease characteristics involving nonliving xenobiotics are primarily secondary to host phenotype and function. In addition, because of individual genetic susceptibilities based not only on major histocompatibility complex differences but also on differences in toxin metabolism, lifestyles, and exposure rates, individuals will react differently to the same chemicals. With these comments in mind it is important to note that there have been associations of a number of xenobiotics with human autoimmune disease, including mercury, iodine, vinyl chloride, canavanine, organic solvents, silica, l-tryptophan, particulates, ultraviolet radiation, and ozone. In addition, there is discussion in the literature that raises the possibility that xenobiotics may also exacerbate an existing autoimmune disease. In this article we discuss these issues and, in particular, the evidence for the role of environmental agents in the initiation or progression of autoimmune conditions. With the worldwide deterioration of the environment, this is a particularly important subject for human health.

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“…Fifty to sixty percent of A/J mice died within 5 days, and another 20% died within two weeks of exposure to OA. This strain exhibited increased serum IgE, IgG, and IgM, and upregulation of IL-10, IL-1α, IL-6, and IFNγ mRNA in the spleen (Bell, 1996;Berking et al, 1998;Bell et al, 1999). The difference in the responses of the various strains of mice tested suggests a genetic component in susceptibility to TOS.…”

Section: Experimental Studies Of Tosmentioning

confidence: 85%

“…Solid arrows represent major pathways and dashed arrows represent alternative pathways. Adapted from Wulferink et al (2001, Lahoz et al (1997), Gelpi et al (2002), Bell et al (1996), and Berking et al (1998). Journal of Immunotoxicology Downloaded from informahealthcare.com by CDL-UC Davis on 11/17/14 factors, and biochemical alterations may be involved in disease development (Aldridge, 1992;Gelpi et al, 2002).…”

Section: Experimental Studies Of Tosmentioning

confidence: 98%

“…MHC class has been used to distinguish autoimmune disease-prone strains and establish a hierarchy in the strength of the immune response, with H-2s as the high responding mice, H-2b as the low responders and H-2a as nonresponders (Berking et al, 1998). MRL/lpr (H-2s) mice develop idiopathic autoimmune diseases and, due to a fatal deletion in the fas gene, are prone to a high degree of apoptosis (Hard, 2002).…”

Section: Experimental Studies Of Tosmentioning

confidence: 99%

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

Patterson

Germolec

2005

Journal of Immunotoxicology

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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.

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Strain-Dependent Cytokine Profile and Susceptibility to Oleic Acid Anilide in a Murine Model of the Toxic Oil Syndrome

Cited by 23 publications

References 27 publications

Pathology of “Toxic Oils” and Selected Metals in the MRL/lpr Mouse

Pathology of “Toxic Oils” and Selected Metals in the MRL/lpr Mouse

Evidence for the role of environmental agents in the initiation or progression of autoimmune conditions.

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

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