IL-8 Downregulation Mediates the Beneficial Effects of Infection-Induced Fever on Breast Cancer Prognosis
Heliang Li,1,2,* Xinyan Liang,1,2,* Jiafan Ma,1,2,* Qiang Liu,1,2 Ying Lin,3 Junpeng Tang,4 Zefang Ren,5 Zhuozhi Liang1,2,6 1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2025-01-01
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| Series: | Journal of Inflammation Research |
| Subjects: | |
| Online Access: | https://www.dovepress.com/il-8-downregulation-mediates-the-beneficial-effects-of-infection-induc-peer-reviewed-fulltext-article-JIR |
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| Summary: | Heliang Li,1,2,* Xinyan Liang,1,2,* Jiafan Ma,1,2,* Qiang Liu,1,2 Ying Lin,3 Junpeng Tang,4 Zefang Ren,5 Zhuozhi Liang1,2,6 1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 2Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 3Breast Disease Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 4Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 5The School of Public Health, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 6Zenith Institute of Medical Sciences, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhuozhi Liang; Zefang Ren, Email liangzhzh6@mail2.sysu.edu.cn; renzef@mail.sysu.edu.cnPurpose: Previous studies have reported that infection-induced fever is associated with improved breast cancer prognosis, potentially through the modulation of cytokines. However, the key cytokines and the underlying mechanisms through which fever exerts its anti-tumor effects remain unclear.Patients and Methods: A total of 794 breast cancer patients were recruited between 2008 and 2017, with follow-up extending until October 31st, 2023. Infection-induced fever was assessed using questionnaires, while a multiplex assay evaluated a panel of 27 cytokines. The mediation effects of various cytokines were analyzed through model-based causal mediation analysis. Additionally, we explored modifications to these mediation effect by examining interactions among the cytokines themselves as well as their interactions with infection-induced fever. Bioinformatic analyses were conducted to elucidate the biological pathways mediating infection-induced fever.Results: The relationship between infection-induced fever and improved breast cancer prognosis was mediated by a decrease in interleukin-8 (IL-8) levels. Furthermore, our findings revealed that the downregulation of IL-8, which mediates the beneficial effects of fever, was antagonized by IL-2, IL12p70 and IL-7. By intersecting the biological pathways influenced by IL-8, alongside those affected by IL-2, IL12p70, or IL-7, we found that these latter cytokines antagonized the mediation effects of IL-8 via regulating critical pathways such as neutrophil degranulation, extracellular matrix organization and asparagine N-linked glycosylation.Conclusion: Infection-induced fever may improve breast cancer prognosis through IL-8 downregulation and the mediation mechanisms may be involved in neutrophil degranulation, extracellular matrix organization and asparagine N-linked glycosylation. Such findings not only provide valuable insights into effectively managing febrile responses for breast cancer patients, but also underscore the therapeutic potential of cytokines in breast cancer patients.Keywords: infection-induced fever, breast cancer, prognosis, cytokines, IL-8 |
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| ISSN: | 1178-7031 |