Immunotoxic response of oleic acid anilide and its hydrolysis products in female MRL^+/+ mice

An epidemic of a multi-systemic disease, known as the toxic oil syndrome (TOS), was caused by consumption of edible oil denatured with 2% aniline. Oleic acid anilide (OAA) has been suggested as one of the most likely etiologic agents responsible for TOS based upon its presence in high quantities in TOS-related oil samples. The aim of this study was to evaluate the immune response of OAA and contribution of its hydrolysis products (aniline and oleic acid) in the immunotoxic response. Female MRL^+/+ mice were treated with equimolar doses of OAA, aniline or oleic acid (0.8 mmol/kg), i.p., twice a week for 6 weeks. The levels of immunoglobulins IgE, IgG and its isotypes (IgG₁, IgG_2a, IgG_2b, and IgG₃), and the appearance of antinuclear antibodies (ANA) were determined in the serum. Exposure to OAA and oleic acid caused significant increases in IgG, IgG₁, IgG _2a, and IgG_2b levels as compared to aniline and control groups, whereas IgG₃ value increased only in OAA-treated mice. The IgE levels in OAA-, aniline-, and oleic acid-treated groups were higher than the controls. Among the various treatment groups, sera from 50% of the OAA-treated mice gave rise to intense homogenous fluorescence patterns on Hep-2 cells, suggesting the presence of significant levels of antinuclear antibodies (ANA). Furthermore, analysis of serum cytokines showed significant increases in G-CSF levels in OAA- and aniline-treated mice. Among the tissues examined, morphological changes were confined to the spleen, which showed increased lymphocyte population in OAA- and aniline-treated mice. These studies indicate that OAA and its hydrolysis products cause perturbations in the immune response, and could contribute to TOS-related immune derangements.