Specialized proresolving mediators (SPRM), which arise from n-3 long-chain
polyunsaturated fatty acids (n-3FA), promote resolution of
inflammation and may help to prevent progression of an acute inflammatory response into chronic
inflammation in patients with
arthritis. Thus, this study is aimed at determining whether systemic
RvE1 treatment reduces
arthritis onset and severity in murine
collagen-induced arthritis (CIA) and spontaneous
cytokine production by human
rheumatoid arthritis (RA) synovial explants. 10-week-old DBA1/J male mice were subjected to CIA and treated systemically with 0.1 μg
RvE1, 1 μg
RvE1, 5 mg/kg anti-TNF (positive control group), PBS (negative control group), or with a combination of 1 μg of
RvE1 plus 5 mg/kg anti-TNF using prophylactic or therapeutic strategies. After CIA immunization, mice were treated twice a week by
RvE1 or anti-TNF for 10 days.
Arthritis development was assessed by visual scoring of paw swelling and histology of ankle joints. Moreover, human RA synovial explants were incubated with 1 nM, 10 nM, or 100 nM of
RvE1, and
cytokine levels (IL-1β, IL-6, IL-8, IL-10, INF-γ, and TNF-α) were measured using Luminex bead array. CIA triggered significant
inflammation in the synovial cavity,
proteoglycan loss, and cartilage and bone destruction in the ankle joints of mice. Prophylactic and therapeutic
RvE1 regimens did not ameliorate CIA incidence and severity. Anti-TNF treatment significantly abrogated signs of joint
inflammation, bone erosion, and
proteoglycan depletion, but additional
RvE1 treatment did not further reduce the anti-TNF-mediated suppression of the disease. Treatment with different concentrations of
RvE1 did not decrease the expression of proinflammatory
cytokines in human RA synovial explants in the studied conditions. Collectively, our findings demonstrated that
RvE1 treatment was not an effective approach to treat CIA in DBA1/J mice in both prophylactic and therapeutic strategies. Furthermore, no effects were noticed when human synovial explants were incubated with different concentrations of
RvE1.