Abstract
Mineral oils are extensively used in our daily life, in food, cosmetics, biomedicine, vaccines and in different industrial applications. However, exposure to these mineral oils has been associated with immune adjuvant effects and the development of autoimmune diseases. Here we investigate the structural impacts of the hydrocarbon oil molecules on their adjuvanticity and autoimmunity. First, we showed that hydrocarbon oil molecules with small atomic differences could result in experimental arthritis in DA rats differing in disease severity, incidence, weight change and serum levels of acute phase proteins. Injection of these hydrocarbon oils resulted in the activation, proliferation and elevated expression of Th1 and especially Th17 cytokines by the T cells, which correlate with the arthritogenicity of the T cells. Furthermore, the more arthritogenic hydrocarbon oils resulted in an increased production of autoantibodies against cartilage joint specific, triple-helical type II collagen epitopes. When injected together with ovalbumin, the more arthritogenic hydrocarbon oils resulted in an increased production of αβ T cell-dependent anti-ovalbumin antibodies. This study shows the arthritogenicity of hydrocarbon oils is associated with their adjuvant properties with implications to not only arthritis research but also other diseases and medical applications such as vaccines in which oil adjuvants are involved.
Highlights
Mineral oils are often used in food, cosmetics, biomedicine and different industrial applications
We showed that atomic differences in the hydrocarbon oil adjuvants could result in dramatic differences in adjuvanticity and autoimmunity, including differences in arthritis induction, acute phase response, immune cell frequency, T cell activation, proliferation and cytokine expression, autoantibody production, and antigen-specific recall response and antibody production
Combining both gene expression and flow cytometry analysis, together with adoptive disease transfer of T cells on day 5 and day 8 after adjuvant administration, we showed the choice of oil adjuvants can have pronounced impact on immune cell responses which resulted in different disease outcomes and the arthritogenicity of hydrocarbon oils is associated with their adjuvant properties
Summary
Mineral oils are often used in food, cosmetics, biomedicine and different industrial applications. These arthritis models include cartilage-restricted antigen-induced arthritis, which use type II collagen (CII), type XI collagen (CXI) or cartilage oligomeric matrix protein (COMP) as the antigen; and mycobacterial adjuvant-induced arthritis (Mbt-AIA), which induces disease by injection of heat-killed mycobacteria emulsified in IFA These arthritis models mimic different aspects of RA and have been very useful for identifying arthritis-regulating loci and genes, many of which could not be detected in the past human genome-wide association studies due to various limitations[7,8]. For adjuvant-induced arthritis models, different immunostimulatory agents have been described to induce polyarthritis in arthritis-susceptible rat strains, such as DA These agents include IFA, which is an undefined mixture of oil molecules (oil-induced arthritis, OIA), and structurally defined hydrocarbon molecules such as pristane (pristane-induced arthritis, PIA), hexadecane (hexadecane-induced arthritis, HXIA) and squalene (squalene-induced arthritis, SIA)[5,6,11,13,14]. We showed that these hydrocarbon adjuvants vary in their stimulatory effects on antigen-specific recall response and antibody production
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