The Endogenous Adjuvant Squalene

pubmed logo adjuvant squalene Autoimmune/Inflammatory Syndrome Induced by Adjuvants ASIA shonefields syndrome Postural Orthostatic Tachycardia With Chronic Fatigue
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The Endogenous Adjuvant Squalene


Squalene is a cholesterol precursor, which stimulates the immune system nonspecifically. We demonstrate that one intradermal injection of this adjuvant lipid can induce joint-specific inflammation in arthritis-prone DA rats. Histopathological and immunohistochemical analyses revealed erosion of bone and cartilage, and that development of polyarthritis coincided with infiltration of αβ+ T cells. Depletion of these cells with anti-αβ TcR monoclonal antibody (R73) resulted in complete recovery, whereas anti-CD8 and anti-γδ TcR injections were ineffective. The apparent dependence on CD4+ T cells suggested a role for genes within the major histocompatibility complex (MHC), and this was concluded from comparative studies of MHC congenic rat strains, in which DA.1H rats were less susceptible than DA rats. Furthermore, LEW.1AV1 and PVG.1AV1 rats with MHC identical to DA rats were arthritis-resistant, demonstrating that non-MHC genes also determine susceptibility. Some of these genetic influences could be linked to previously described arthritis susceptibility loci in an F2 intercross between DA and LEW.1AV1 rats (ie, Cia3Oia2 and Cia5). Interestingly, some F2 hybrid rats developed chronic arthritis, a phenotype not apparent in the parental inbred strains. Our demonstration that an autoadjuvant can trigger chronic, immune-mediated joint-specific inflammation may give clues to the pathogenesis of rheumatoid arthritis, and it raises new questions concerning the role of endogenous molecules with adjuvant properties in chronic inflammatory diseases.

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Kevin is a former Navy Aviation Machinist Mate, and Former Department of Defense Systems Engineer. Besides being very mechanically inclined, he holds a Bachelors of Computer Science. Kevin is a vaccine injury veteran and spends his spare time helping Operation Truth with their mission.