This study tested the hypothesis that
ethyl pyruvate (EP), a simple aliphatic
ester with anti-inflammatory effects, can reduce
type II collagen-induced mouse
arthritis (CIA). DBA/1J mice were used for the study, developing erosive hind paw
arthritis when immunized with CII in an
emulsion in complete
Freund?s adjuvant (CFA). The incidence of CIA was 100 percent by day 28 in the CII-challenged mice, and the severity of CIA progressed over a 35-day period with radiographic evaluation revealing focal resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint margins. EP-treatment (40 mg/kg/day i.p.) starting at the onset of
arthritis (day 25) ameliorated the clinical signs at days 26-35 and improved histological status in the joint and paw. Immunohistochemical analysis for
nitrotyrosine,
poly (ADP-ribose) (PAR),
inducible nitric oxide synthase (iNOS) revealed a positive staining in inflamed joints from mice subjected to CIA, while no staining was observed for HO-1 and Nrf-2 in the same group. The degree of staining for
nitrotyrosine, PAR, iNOS, was significantly reduced in CII-challenged mice treated with the EP. Immuno-positive-staining for HO-1 and Nrf-2 was observed instead, in joints obtained from the EP-treated group. Plasma levels of TNF-α,
IL-6 and the joint tissue levels of
macrophage inflammatory protein (MIP)-1α and MIP-2 were also significantly reduced by EP treatment. Thirty-five days after immunization, EP-treatment significantly increased plasma levels of
IL-10. These data demonstrate that EP treatment exerts an anti-inflammatory effect during chronic
inflammation and is able to ameliorate the tissue damage associated with CIA.