Challenges of modeling pristane-induced lupus in non-human primates

A lupus-like condition induced by intraperitoneal administration of pristane (2,6,10,14-tetramethylpentadecane) in mice is widely used as a model of systemic lupus erythematosus (SLE). Due to their phylogenetic distance from humans, murine models are not always suitable tool for studying the specific activity of therapeutic agents and the pathogenesis of SLE. In order to overcome species-specific limitations of murine models, this approach was tested in non-human primates-cynomolgus monkeys (Macaca fascicularis). Two intraperitoneal injections at a dose of 3.5 mL/kg, administered at weeks 1 and 23, recapitulated SLE features, including: production of antinuclear autoantibodies (ANA), membranoproliferative glomerulonephritis with immune complex (IC) deposition in the glomeruli. However, from week 27 five of eight pristane-treated monkeys developed progressive respiratory failure. Two of these died at week 28 and the remaining were euthanized at week 32. The histology of the monkey lungs suggested exogenous lipoid pneumonia. Thus, while pristane induced serological autoimmunity and characteristic renal manifestations in Macaca fascicularis, the consequent lipoid pneumonia limited the observation period and prevented comprehensive evaluation of SLE manifestations beyond 32 weeks.