Authors: Diego A Lema, Monica Talor, Sara Rattik, Caitriona Gronberg, David Liberg, Daniela Cihakova
Published: 2022-11-14
DOI: 10.1161/res.131.suppl_1.p3061
Source: Full article
IL-1, IL-33 and IL-36 have complementary, pro-inflammatory roles during the immune response that promote autoimmune diseases, particularly myocarditis. While antibodies that neutralize circulating cytokines exist, we hypothesized that blockade of their shared co-receptor, IL-1 receptor accessory protein (IL1RAP), would exhibit a more potent and broader anti-inflammatory profile. The CAN10 antibody blocks IL1RAP and is currently under development for treating severe autoimmune and inflammatory diseases. To investigate if IL1RAP blockade is an effective treatment of cardiac inflammation, we induced autoimmune viral myocarditis in 8-week-old Balb/c male mice with Coxsackievirus B3 and treated them with mCAN10, an anti-mouse IL1RAP monoclonal antibody. Mice were euthanized at day 10, the peak of acute inflammation in the heart. IL1RAP blockade reduced the severity of myocarditis at this timepoint when compared to isotype, saline or IL-1 receptor antagonist (IL1RA) treatment (the gold standard in IL-1 receptor blockade), without affecting viral clearance from the heart. Spectral flow cytometry of heart immune populations revealed that mCAN10 significantly reduced the number of infiltrating leukocytes of broad populations, especially effector CD4