To determine whether elevated serum lipid levels resulting from feeding animals a high‐fat diet can affect the inflammatory process in C57BL/6 (B6) wild‐type (WT) and B6 ApoE^−/− mouse models of collagen‐induced arthritis (CIA).

Male B6 WT or ApoE^−/− mice were fed either a normal chow diet or a high‐fat diet. CIA was induced in mice at 12 weeks of age using type II chicken collagen, Freund's complete adjuvant, and, on occasion, a lipopolysaccharide boost. Expression levels of autoantibodies and cytokines were measured using enzyme‐linked immunosorbent assay and multiplex assay, respectively.

Whereas B6 WT mice developed severe articular inflammation after collagen immunization, ApoE^−/− mice developed no clinical or histologic evidence of disease regardless of whether they had been fed a high‐fat diet or a normal chow diet. The fact that arthritis was not present in ApoE^−/− mice did not result from inadequate production of serum IgG2a collagen antibodies, since levels observed in ApoE^−/− mice were similar to those observed in arthritic B6 WT control mice. Critically, development of atherosclerosis in ApoE^−/− mice was not affected by the CIA protocol.

Our findings suggest that ApoE^−/− mice are resistant to the development of CIA. Intriguingly, induction of host autoimmunity in the absence of articular inflammation had no effect on atherosclerosis progression, suggesting that articular inflammatory load may be a critical risk factor in vascular pathology.