130. Nicotinamide alleviates preeclampsia-like features and lupus nephritis in pregnant MRL/lpr mice treated with LPS

Introduction Systemic Lupus Erythematosus (SLE) increases the risk of unfavorable pregnancy outcomes including preterm birth and preeclampsia (PE). Flare-up of SLE during pregnancy or after birth is also problematic. TLR4 signaling is known to exacerbate both SLE and pregnancy. We have shown that nicotinamide (NAM), a non-teratogenic amide of vitamin B3, reduces inflammation and oxidative stress, and improves PE-like phenotype in mouse models of PE (Takahashi et al. PNAS 2016). Objective The aim of the present study is to establish a mouse model to study pathogenesis and treatment of SLE patients suffering from PE, and to test whether nicotinamide (NAM) is beneficial to preeclamptic SLE mice. Methods and results We administered low dose LPS, a TLR4 ligand, to pregnant lupus-prone MRL/lpr mice, and analyzed maternal and fetal outcomes. LPS increased blood pressure, caused fetal growth restriction (FGR), and exacerbated glomerulonephritis in MRL/lpr-LPS mouse. We conclude that this is a suitable model to study pathogenesis of pregnancy in SLE. We next examined a therapeutic effect of NAM on the pregnancy outcome and lupus nephritis in pregnant MRL/lpr mice given LPS. NAM (500 mg/kg) was administered on 13.5–17.5 dpc, and data and samples were collected on 18.5 dpc. NAM decreased maternal blood pressure, prolonged pregnancy period, and corrected FGR. NAM significantly improved glomerular injury and inflammatory cell infiltration, which was accompanied by reduced expression of inflammatory cytokines in their kidneys. NAM also decreased the level of plasma anti-dsDNA antibody and lymphadenopathy. Discussion NAM alleviates PE-like features, FGR, and lupus activity in MRL/lpr-LPS model. NAM may be a novel therapeutic option to benefit pregnant SLE patients.