Background/Purpose: Kawasaki disease (KD), is the leading cause of acquired heart disease in childhood. Up to 20% of patients may develop coronary artery lesions (CAL) despite standard of care treatment with intravenous immunoglobulin (IVIg).

Murine and patient data indicate Interleukin-1 (IL-1) contributes to CALs. Proton pump inhibitors (PPI), a class of medications used to limit gastric acid secretion, have also been shown to have anti-inflammatory properties: 1) decreasing macrophage IL-1β secretion in vitro and 2) improving clinical outcomes in IL-1 mediated murine models.

This study aims to determine if PPIs inhibit IL-1β production and resulting CAL in the Lactobacillus casei cell wall extract (LCWE) induced coronary arteritis murine model of KD.

Methods: Bone marrow derived macrophages (BMDMs) were obtained from adult mice and stimulated with Pam3Cys and Lactobacillus casei cell wall extract (LCWE), in the presence or absence of PPIs. To exclude toxic effects, viability was tested via flow cytometry and trypan blue exclusion. Electrolyte flux was measured via fluorescent imaging plate reader. In vivo, KD was induced by intraperitoneal LCWE injection. Mice were injected with LCWE alone, LCWE+PPI, saline or PPI alone. Coronary artery inflammation was scored by a blinded pathologist. Using ELISA, serum IL-1β and NT-proBNP were measured.

Results: Following stimulation with either Pam3Cys or LCWE, PPIs inhibited BMDM IL-1β production in a dose-dependent and drug class independent manner. Inflammasome activation was prevented by PPI inhibition of signal two. In vivo, compared to untreated KD diseased mice, those treated with PPI were shown to have significantly reduced coronary artery inflammation.

Conclusion: IL-1 is essential for the development of LCWE induced murine KD and anti-IL-1 therapy have been shown to prevent myocardial inflammatory changes. Our data indicate that PPIs have extra-gastrointestinal anti-inflammatory properties in a murine KD model preventing IL-1 induced coronary artery inflammation. PPIs may be a novel inexpensive, oral, and safe adjuvant anti-IL-1 medication to treat KD.

« Back to ACR Convergence 2021

ACR Meeting Abstracts - https://acrabstracts.org/abstract/proton-pump-inhibitors-suppress-il-1-mediated-carditis-in-a-murine-model-of-kawasaki-disease/