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Exploring strategies to modulate pathological cytokine storms can effectively prevent the development of severe coronavirus infection\u2010induced pneumonia. Treatment with interleukin\u201037 (IL\u201037), an anti\u2010inflammatory factor, has unique anti\u2010inflammatory and antiviral effects on infections caused by various pathogens. In this study, we investigated the effect of IL\u201037 treatment on the SARS\u2010CoV\u20102 Omicron\u2010infection induced inflammatory response and its molecular mechanism. Our results demonstrated that IL\u201037 treatment effectively alleviated symptoms, reduced viral loads, suppressed the production of proinflammatory cytokines and chemokines both systemically (in serum) and locally (in the lungs), and attenuated lung lesions and inflammatory cell infiltration in Omicron\u2010infected mice. The suppressed proinflammatory factors were macrophage\u2010related, particularly CCL3 and CCL4, which were significantly inhibited. Furthermore, treatment with IL\u201037 significantly reduced the proportion of M1\u2010type macrophages in lungs of Omicron\u2010infected mice. In addition, we found that IL\u201037 targeted M1 macrophages through modulation of the NF\u2010\u03baB signaling pathway to suppress the production of proinflammtory factors during Omicron infection. This study elucidated the anti\u2010inflammatory effect of IL\u201037 treatment on the Omicron\u2010induced inflammatory response while identifying its specific target site, thereby providing fundamental insights for exploring potential clinical therapeutic interventions.<\/jats:p>","DOI":"10.1002\/mco2.70229","type":"journal-article","created":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T02:42:15Z","timestamp":1748745735000},"source":"Crossref","is-referenced-by-count":4,"title":["IL\u201037 Mitigates the Inflammatory Response in Macrophages Induced by SARS\u2010CoV\u20102 Omicron Infection Through the NF\u2010\u03baB Signaling Pathway"],"prefix":"10.1002","volume":"6","author":[{"given":"Feifei","family":"Qi","sequence":"first","affiliation":[{"name":"Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, NHC Key Laboratory of Comparative Medicine, Institute of Laboratory Animal Science, CAMS &amp;PUMC  Beijing China"},{"name":"National Center 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