{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T16:01:17Z","timestamp":1774627277851,"version":"3.50.1"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"National Research Institute for Child Health and Development"},{"name":"Japan Kawasaki Disease Research Center"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Kawasaki disease (KD) is the most common childhood vasculitis. Approximately 25% of KD patients are refractory to standard intravenous immunoglobulin (IVIG) therapy and frequently develop coronary artery lesions (CAL) that result in long-term complications. Transcriptome studies utilizing blood cells from KD patients and reported animal model studies had identified interleukin (IL)-1\u03b2 as a crucial component of an essential immune pathway in the formation of CAL. We previously reported that high-dose immunoglobulin G (IgG) treatment completely inhibited tumor necrosis factor (TNF)-\u03b1-stimulated inflammatory responses in an in vitro human coronary artery endothelial cells (HCAECs) model. Here, we show that IL-1\u03b2, but not TNF-\u03b1, stimulation markedly induced nuclear protein expression of NF-kappa-B inhibitor zeta (I\u03baB\u03b6) in HCAECs. It is of particular significance that IL-1\u03b2-induced I\u03baB\u03b6 expression is entirely refractory to high-dose IgG treatment. Therefore, I\u03baB\u03b6 may be a critical factor in the IVIG-resistant vascular inflammatory responses in severe KD. Itaconate is a Krebs cycle-derived metabolite with several immunomodulatory effects. Dimethyl itaconate (DI), a membrane-permeable derivative of itaconate, can significantly suppress IL-1\u03b2-induced I\u03baB\u03b6 expression in HCAECs. DI is an analog of dimethyl fumarate (DMF), which is already in clinical use for some diseases. Like DI, DMF suppressed IL-1\u03b2-induced I\u03baB\u03b6 expression and subsequent production of inflammatory cytokines, including IL-6 and G-CSF. This study identified I\u03baB\u03b6 as an essential inflammatory factor in IVIG-resistant inflammatory responses in HCAECs. Immunomodulatory substances, such as DI and\/or DMF, may be therapeutically exploited as a novel drug to alleviate inflammation in severe IVIG-resistant KD patients.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf245","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T23:55:05Z","timestamp":1758326105000},"source":"Crossref","is-referenced-by-count":1,"title":["Dimethyl itaconate attenuates IL-1-induced IVIG-resistant inflammation in a coronary artery cell model of Kawasaki disease"],"prefix":"10.1093","volume":"215","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3535-4103","authenticated-orcid":false,"given":"Ikuyo","family":"Ito","sequence":"first","affiliation":[{"name":"Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development , Tokyo 157-8535,","place":["Japan"]},{"name":"Department of Pediatrics, School of Medicine, Yokohama City University , Kanagawa 236-0004,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shokei","family":"Murakami","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development , Tokyo 157-8535,","place":["Japan"]},{"name":"Department of Pediatrics, Toyama University School of Medicine , Toyama 930-0194,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development , Tokyo 157-8535,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuichi","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine, Yokohama City University , Kanagawa 236-0004,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Advanced Medicine for Infections, National Research Institute for Child Health and Development , Tokyo 157-8535,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenichiro","family":"Motomura","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development , Tokyo 157-8535,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideaki","family":"Morita","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development , Tokyo 157-8535,","place":["Japan"]},{"name":"Allergy Center, National Center for Child Health and Development , Tokyo 157-8535,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development , Tokyo 157-8535,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akio","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development , Tokyo 157-8535,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,9,16]]},"reference":[{"key":"2026012707073324700_vkaf245-B1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1542\/peds.54.3.271","article-title":"A new infantile acute febrile mucocutaneous lymph node syndrome (MLNS) prevailing in 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