Abstract O.26: Angiotensin Receptor Blocker, Losartan suppresses coronary arteritis in a Murine Model of Kawasaki Disease. -Effectiveness of IVIG versus Losartan-
Background: Although intravenous immunoglobulin (IVIG) is an established treatment for Kawasaki disease (KD), 5 % of KD patients treated with IVIG still have coronary involvement. Angiotensin receptor blockers (ARBs), beside their antihypertensive effects, also suppress cell infiltration in atherosclerosis. However, the efficacy of ARB for KD has not been established.
Objective: We aimed to elucidate if ARB ameliorates coronary arteritis (CA) in a murine model of KD, introduced by Lactobacillus casei wall extract (LCWE). We also aimed to verify whether ARB’s effects are different from those of IVIG.
Method: 4-week-old male mice were intraperitoneally injected with LCWE (L, n=15) or PBS (P, n=15). 5 days later, those mice were given IVIG (1g/kg, L+IVIG, n=8), or ARB (losartan 100mg/L in drinking water for 2 wks, L+ARB, n=18). 2 weeks after LCWE injection, histological assessment of the heart and measurement of plasma cytokine levels were performed. IL-6 and mannose receptor (MR) mRNA expressions in the aortic root were studied (n=5 each group) in an additional experiment.
Results: CA score was significantly increased by LCWE (L: 8.3±0.5 vs. P: 2.9±0.5, p<0.0001). ARB significantly ameliorated CA (L+ARB: 5.1±0.7 vs. L, p=0.008). The effect of IVIG on CA was milder and not significant (L+IVIG: 6.0±0.9 vs. L). Of note, macrophage infiltration was dramatically decreased by ARB but not by IVIG. IVIG treatment ameliorated serum levels of IL-1β, IL-10 and TNF-α in a milder fashion than ARB. Interestingly, serum IL-6 level was suppressed by ARB, but not by IVIG. Locally up-regulated mRNAs of IL-6 and MR were significantly ameliorated by ARB, with milder effects by IVIG.
Conclusions: ARB, rather than IVIG, exerts powerful anti-CA effects with suppressing local macrophage infiltration and systemic/local inflammatory cytokines. Thus, ARB potentially exerts additive anti-CA effects in KD under IVIG treatment.
Author Disclosures: E. Suganuma: None.
- © 2015 by American Heart Association, Inc.