IL‐37 Mitigates the Inflammatory Response in Macrophages Induced by SARS‐CoV‐2 Omicron Infection Through the NF‐κB Signaling Pathway

ABSTRACT The expression levels of macrophage‐associated cytokines are significantly greater in COVID‐19 patients than in healthy individuals. Exploring strategies to modulate pathological cytokine storms can effectively prevent the development of severe coronavirus infection‐induced pneumonia. Treat...

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Main Authors: Feifei Qi, Yiwei Yan, Mingya Liu, Qi Lv, Yanfeng Xu, Ming Liu, Fengdi Li, Ran Deng, Xujian Liang, Shuyue Li, Guocui Mou, Linlin Bao
Format: Article
Language:English
Published: Wiley 2025-06-01
Series:MedComm
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Online Access:https://doi.org/10.1002/mco2.70229
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author Feifei Qi
Yiwei Yan
Mingya Liu
Qi Lv
Yanfeng Xu
Ming Liu
Fengdi Li
Ran Deng
Xujian Liang
Shuyue Li
Guocui Mou
Linlin Bao
author_facet Feifei Qi
Yiwei Yan
Mingya Liu
Qi Lv
Yanfeng Xu
Ming Liu
Fengdi Li
Ran Deng
Xujian Liang
Shuyue Li
Guocui Mou
Linlin Bao
author_sort Feifei Qi
collection DOAJ
description ABSTRACT The expression levels of macrophage‐associated cytokines are significantly greater in COVID‐19 patients than in healthy individuals. Exploring strategies to modulate pathological cytokine storms can effectively prevent the development of severe coronavirus infection‐induced pneumonia. Treatment with interleukin‐37 (IL‐37), an anti‐inflammatory factor, has unique anti‐inflammatory and antiviral effects on infections caused by various pathogens. In this study, we investigated the effect of IL‐37 treatment on the SARS‐CoV‐2 Omicron‐infection induced inflammatory response and its molecular mechanism. Our results demonstrated that IL‐37 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‐infected mice. The suppressed proinflammatory factors were macrophage‐related, particularly CCL3 and CCL4, which were significantly inhibited. Furthermore, treatment with IL‐37 significantly reduced the proportion of M1‐type macrophages in lungs of Omicron‐infected mice. In addition, we found that IL‐37 targeted M1 macrophages through modulation of the NF‐κB signaling pathway to suppress the production of proinflammtory factors during Omicron infection. This study elucidated the anti‐inflammatory effect of IL‐37 treatment on the Omicron‐induced inflammatory response while identifying its specific target site, thereby providing fundamental insights for exploring potential clinical therapeutic interventions.
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spelling doaj-art-0ac8a7a67dde46b19574690df562632a2025-08-20T03:44:01ZengWileyMedComm2688-26632025-06-0166n/an/a10.1002/mco2.70229IL‐37 Mitigates the Inflammatory Response in Macrophages Induced by SARS‐CoV‐2 Omicron Infection Through the NF‐κB Signaling PathwayFeifei Qi0Yiwei Yan1Mingya Liu2Qi Lv3Yanfeng Xu4Ming Liu5Fengdi Li6Ran Deng7Xujian Liang8Shuyue Li9Guocui Mou10Linlin Bao11Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, NHC Key Laboratory of Comparative Medicine, Institute of Laboratory Animal Science, CAMS &PUMC Beijing ChinaBeijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, NHC Key Laboratory of Comparative Medicine, Institute of Laboratory Animal Science, CAMS &PUMC Beijing ChinaBeijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, NHC Key Laboratory of Comparative Medicine, Institute of Laboratory Animal Science, CAMS &PUMC Beijing ChinaBeijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, NHC Key Laboratory of Comparative Medicine, Institute of Laboratory Animal Science, CAMS &PUMC Beijing ChinaBeijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, NHC Key Laboratory of Comparative Medicine, Institute of Laboratory Animal Science, CAMS &PUMC Beijing ChinaBeijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, NHC Key Laboratory of Comparative Medicine, Institute of Laboratory Animal Science, CAMS &PUMC Beijing ChinaBeijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, NHC Key Laboratory of Comparative Medicine, Institute of Laboratory Animal Science, CAMS &PUMC Beijing ChinaBeijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, NHC Key Laboratory of Comparative Medicine, Institute of Laboratory Animal Science, CAMS &PUMC Beijing ChinaBeijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, NHC Key Laboratory of Comparative Medicine, Institute of Laboratory Animal Science, CAMS &PUMC Beijing ChinaBeijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, NHC Key Laboratory of Comparative Medicine, Institute of Laboratory Animal Science, CAMS &PUMC Beijing ChinaBeijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, NHC Key Laboratory of Comparative Medicine, Institute of Laboratory Animal Science, CAMS &PUMC Beijing ChinaBeijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, NHC Key Laboratory of Comparative Medicine, Institute of Laboratory Animal Science, CAMS &PUMC Beijing ChinaABSTRACT The expression levels of macrophage‐associated cytokines are significantly greater in COVID‐19 patients than in healthy individuals. Exploring strategies to modulate pathological cytokine storms can effectively prevent the development of severe coronavirus infection‐induced pneumonia. Treatment with interleukin‐37 (IL‐37), an anti‐inflammatory factor, has unique anti‐inflammatory and antiviral effects on infections caused by various pathogens. In this study, we investigated the effect of IL‐37 treatment on the SARS‐CoV‐2 Omicron‐infection induced inflammatory response and its molecular mechanism. Our results demonstrated that IL‐37 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‐infected mice. The suppressed proinflammatory factors were macrophage‐related, particularly CCL3 and CCL4, which were significantly inhibited. Furthermore, treatment with IL‐37 significantly reduced the proportion of M1‐type macrophages in lungs of Omicron‐infected mice. In addition, we found that IL‐37 targeted M1 macrophages through modulation of the NF‐κB signaling pathway to suppress the production of proinflammtory factors during Omicron infection. This study elucidated the anti‐inflammatory effect of IL‐37 treatment on the Omicron‐induced inflammatory response while identifying its specific target site, thereby providing fundamental insights for exploring potential clinical therapeutic interventions.https://doi.org/10.1002/mco2.70229IL‐37inflammatory responsemacrophagesNF‐κBomicron
spellingShingle Feifei Qi
Yiwei Yan
Mingya Liu
Qi Lv
Yanfeng Xu
Ming Liu
Fengdi Li
Ran Deng
Xujian Liang
Shuyue Li
Guocui Mou
Linlin Bao
IL‐37 Mitigates the Inflammatory Response in Macrophages Induced by SARS‐CoV‐2 Omicron Infection Through the NF‐κB Signaling Pathway
MedComm
IL‐37
inflammatory response
macrophages
NF‐κB
omicron
title IL‐37 Mitigates the Inflammatory Response in Macrophages Induced by SARS‐CoV‐2 Omicron Infection Through the NF‐κB Signaling Pathway
title_full IL‐37 Mitigates the Inflammatory Response in Macrophages Induced by SARS‐CoV‐2 Omicron Infection Through the NF‐κB Signaling Pathway
title_fullStr IL‐37 Mitigates the Inflammatory Response in Macrophages Induced by SARS‐CoV‐2 Omicron Infection Through the NF‐κB Signaling Pathway
title_full_unstemmed IL‐37 Mitigates the Inflammatory Response in Macrophages Induced by SARS‐CoV‐2 Omicron Infection Through the NF‐κB Signaling Pathway
title_short IL‐37 Mitigates the Inflammatory Response in Macrophages Induced by SARS‐CoV‐2 Omicron Infection Through the NF‐κB Signaling Pathway
title_sort il 37 mitigates the inflammatory response in macrophages induced by sars cov 2 omicron infection through the nf κb signaling pathway
topic IL‐37
inflammatory response
macrophages
NF‐κB
omicron
url https://doi.org/10.1002/mco2.70229
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