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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Dove Medical Press
2025-01-01
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| Series: | Journal of Inflammation Research |
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| author | Li H Liang X Ma J Liu Q Lin Y Tang J Ren Z Liang Z |
| author_facet | Li H Liang X Ma J Liu Q Lin Y Tang J Ren Z Liang Z |
| author_sort | Li H |
| collection | DOAJ |
| description | 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 |
| format | Article |
| id | doaj-art-a4f3de8f1cc14cb28567f2ee5929fe55 |
| institution | Kabale University |
| issn | 1178-7031 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Journal of Inflammation Research |
| spelling | doaj-art-a4f3de8f1cc14cb28567f2ee5929fe552025-01-09T16:58:34ZengDove Medical PressJournal of Inflammation Research1178-70312025-01-01Volume 1840541999080IL-8 Downregulation Mediates the Beneficial Effects of Infection-Induced Fever on Breast Cancer PrognosisLi HLiang XMa JLiu QLin YTang JRen ZLiang ZHeliang 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-8https://www.dovepress.com/il-8-downregulation-mediates-the-beneficial-effects-of-infection-induc-peer-reviewed-fulltext-article-JIRinfection-induced feverbreast cancerprognosiscytokinesil-8 |
| spellingShingle | Li H Liang X Ma J Liu Q Lin Y Tang J Ren Z Liang Z IL-8 Downregulation Mediates the Beneficial Effects of Infection-Induced Fever on Breast Cancer Prognosis Journal of Inflammation Research infection-induced fever breast cancer prognosis cytokines il-8 |
| title | IL-8 Downregulation Mediates the Beneficial Effects of Infection-Induced Fever on Breast Cancer Prognosis |
| title_full | IL-8 Downregulation Mediates the Beneficial Effects of Infection-Induced Fever on Breast Cancer Prognosis |
| title_fullStr | IL-8 Downregulation Mediates the Beneficial Effects of Infection-Induced Fever on Breast Cancer Prognosis |
| title_full_unstemmed | IL-8 Downregulation Mediates the Beneficial Effects of Infection-Induced Fever on Breast Cancer Prognosis |
| title_short | IL-8 Downregulation Mediates the Beneficial Effects of Infection-Induced Fever on Breast Cancer Prognosis |
| title_sort | il 8 downregulation mediates the beneficial effects of infection induced fever on breast cancer prognosis |
| topic | infection-induced fever breast cancer prognosis cytokines il-8 |
| url | https://www.dovepress.com/il-8-downregulation-mediates-the-beneficial-effects-of-infection-induc-peer-reviewed-fulltext-article-JIR |
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