Curcumin Improves Autoimmunity in Female Mice with SLE

Abstract

Systemic lupus erythematosus (SLE) is a chronic multi‐system autoimmune disease characterized by the presence of circulating autoantibodies, inflammation, hypertension, renal injury, and cardiovascular disease. Current immunosuppressive therapies often impose unwanted side effects leaving patients searching for alternative therapeutic options. Curcumin has been used in Eastern medicine for its natural anti‐inflammatory and antioxidant properties. We hypothesize that the administration of curcumin will lessen renal inflammation and injury in female mice with SLE.Female NZBWF1 mice, an established experimental model of SLE, and female NZW (control) mice were administered curcumin (500 mg/kg/day) or corn oil (vehicle) by oral gavage for 14 days. This design is based on previously published experimental data using curcumin in mice. Plasma blood urea nitrogen (BUN), a clinical marker of renal function, was assessed at baseline (26 weeks of age) and again at the end of the study (28 weeks of age). To assess immune activity, we measured circulating anti‐dsDNA IgG autoantibodies, spleen weight, and used flow cytometric analyses of peripheral blood leukocytes to assess circulating B lymphocytes at the same time points.Compared with vehicle treated SLE mice, curcumin treated mice with SLE have significantly lower BUN at 28 weeks of age (13.7 ± 0.6 mg/dL SLE‐curcumin, n=14 vs. 36.2 ± 11.4 mg/dL SLE‐vehicle, n=5) (P = 0.0030). As expected, spleen weights are increased in female mice with SLE. However, curcumin treated SLE mice at 28 weeks of age have lower spleen weights compared to SLE vehicle treated mice (0.114 ± 0.009 g SLE‐curcumin, n=14 vs. 0.212 ± 0.03 g SLE‐vehicle, n=5) (P = 0.0008). In addition, the percentage of circulating CD45R+ B cells are decreased at 28 weeks of age in SLE curcumin treated mice compared to vehicle treated SLE mice (5.6 ± 1.6% SLE‐curcumin, n=4 vs. 36.4 ± 9.5% SLE‐vehicle, n=10) (P = 0.068). Despite fewer circulating CD45R+ B cells, plasma levels of anti‐dsDNA IgG autoantibodies are unchanged in curcumin treated mice with SLE compared to vehicle treated mice with SLE. These data suggest that curcumin modulates autoimmune activity and may lessen renal injury in female mice with SLE.Support or Funding InformationResearch reported in this publication was supported by the NIGMS of the NIH (5U54GM115428 and P20GM104357), NHLBI of the NIH (P01HL051971), VA Merit (BX002604‐01A2), and AHA pre‐doctoral fellowship (19PRE34380830).