Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
March-2026 Volume 33 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
March-2026 Volume 33 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review Open Access

Interleukin‑6 and ischemic stroke: From mechanisms to clinical prospects (Review)

  • Authors:
    • Xinyue Wang
    • Xiaohang Zhang
    • Jianing Lin
    • Ping Lin
  • View Affiliations / Copyright

    Affiliations: Department of Neurology, Xinhua Hospital Affiliated to Dalian University, Dalian, Liaoning 116021, P.R. China, Department of Rehabilitation, Xinhua Hospital Affiliated to Dalian University, Dalian, Liaoning 116021, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 80
    |
    Published online on: January 5, 2026
       https://doi.org/10.3892/mmr.2026.13790
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:


Abstract

Neuroinflammation is a central component of the pathophysiology of ischemic stroke (IS). Suppressing excessive inflammatory responses after stroke can markedly improve patient outcomes. Interleukin‑6 (IL‑6), a key mediator of the inflammatory cascade, serves a notable role in the pathological process of acute IS through multiple mechanisms. Elevated serum IL‑6 levels serve as an important biomarker for predicting the onset and recurrence of IS and are closely associated with disease severity and prognosis. Anti‑inflammatory interventions are notably important during the acute phase and secondary prevention of stroke. Currently, therapeutic strategies targeting the IL‑6/IL‑6R signaling axis are under investigation and have shown promising clinical potential. The present review summarizes the important role of IL‑6 in neuroinflammation associated with IS, its association with disease severity and prognosis and previous advances in anti‑inflammatory therapeutic strategies targeting the IL‑6/IL‑6R pathway during both the acute phase and secondary prevention of IS.
View Figures

Figure 1

AIS-related pathological alterations
within and beyond the brain. (A) Impaired cerebral energy
metabolism. (B) Excitotoxic effects of Glu at synaptic sites. (C)
Extracerebral pathological alterations, including autonomic
dysfunction, hyperactivation of the HPA axis and systemic immune
dysregulation. (D) Increased neuronal apoptosis. (E) Oxidative
stress-induced neuronal injury. (F) Excessive neuroinflammation.
Created with BioRender.com and used with permission under
BioRender's Academic License. ATP, adenosine triphosphate; Glu,
glutamate; ROS, reactive oxygen species; DAMPs, damage-associated
molecular patterns; HPA, hypothalamic/pituitary/adrenal axis; AIS,
acute ischemic stroke; HPA, hypothalamic/pituitary/adrenal.

Figure 2

Inflammatory response in AIS. (A)
Following cerebral blood flow interruption, ischemic neurons
release DAMPs, which activate resident glial cells and induce the
secretion of numerous inflammatory mediators. This cascade
upregulates chemokines and adhesion molecules, leading to BBB
disruption. (B) DAMPs activate TLR2 and TLR4, triggering MYD88- and
TRIF-dependent signaling pathways that converge on NF-κB
activation, thereby promoting the expression of inflammatory
cytokines such as IL-1β, IL-6 and TNF-α. (C) Pro-inflammatory
cytokines activate the JAK/STAT3 pathway, amplifying the
inflammatory response and driving microglial polarization toward
the M1 phenotype. (D) IL-6 further acts on vascular endothelial
cells to promote atherosclerotic processes. Created with
BioRender.com and used with permission under BioRender's Academic
License. AIS, acute ischemic stroke; DAMPs, damage-associated
molecular patterns; BBB, blood-brain barrier; TLR, Toll-like
receptor; TRIF, TIR domain-containing adapter molecule 1; JAK,
Janus kinase.
View References

1 

Wang H, Yu X, Guo J, Ma S, Liu Y, Hu Y, Li J, Song Y and Zou Z: Burden of cardiovascular disease among the Western Pacific region and its association with human resources for health, 1990–2021: A systematic analysis of the global burden of disease study 2021. Lancet Reg Health West Pac. 51:1011952024.PubMed/NCBI

2 

Ji C, Ge X, Zhang J and Tong H: The stroke burden in china and its long-term trends: Insights from the global burden of disease (GBD) study 1990–2021. Nutr Metab Cardiovasc Dis. 35:1038482025. View Article : Google Scholar : PubMed/NCBI

3 

Fu Y, Liu Q, Anrather J and Shi FD: Immune interventions in stroke. Nat Rev Neurol. 11:524–535. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Li M, Li Z, Yao Y, Jin WN, Wood K, Liu Q, Shi FD and Hao J: Astrocyte-derived interleukin-15 exacerbates ischemic brain injury via propagation of cellular immunity. Proc Natl Acad Sci USA. 114:E396–E405. 2017.PubMed/NCBI

5 

Zhang F, Yan C, Wei C, Yao Y, Ma X, Gong Z, Liu S, Zang D, Chen J, Shi FD and Hao J: Vinpocetine inhibits NF-κB-dependent inflammation in acute ischemic stroke patients. Transl Stroke Res. 9:174–184. 2018. View Article : Google Scholar : PubMed/NCBI

6 

Endres M, Moro MA, Nolte CH, Dames C, Buckwalter MS and Meisel A: Immune pathways in etiology, acute phase, and chronic sequelae of ischemic stroke. Circ Res. 130:1167–1186. 2022. View Article : Google Scholar : PubMed/NCBI

7 

Zietz A, Gorey S, Kelly PJ, Katan M and McCabe JJ: Targeting inflammation to reduce recurrent stroke. Int J Stroke. 19:379–387. 2024. View Article : Google Scholar : PubMed/NCBI

8 

Pawluk H, Woźniak A, Tafelska-Kaczmarek A, Kosinska A, Pawluk M, Sergot K, Grochowalska R and Kołodziejska R: The role of IL-6 in ischemic stroke. Biomolecules. 15:4702025. View Article : Google Scholar : PubMed/NCBI

9 

Cui P, McCullough LD and Hao J: Brain to periphery in acute ischemic stroke: Mechanisms and clinical significance. Front Neuroendocrinol. 63:1009322021. View Article : Google Scholar : PubMed/NCBI

10 

Stanzione R, Forte M, Cotugno M, Bianchi F, Marchitti S and Rubattu S: Role of DAMPs and of leukocytes infiltration in ischemic stroke: Insights from animal models and translation to the human disease. Cell Mol Neurobiol. 42:545–556. 2022. View Article : Google Scholar : PubMed/NCBI

11 

Kumari S, Dhapola R, Sharma P, Nagar P, Medhi B and HariKrishnaReddy D: The impact of cytokines in neuroinflammation-mediated stroke. Cytokine Growth Factor Rev. 78:105–119. 2024. View Article : Google Scholar : PubMed/NCBI

12 

Lai TW, Zhang S and Wang YT: Excitotoxicity and stroke: Identifying novel targets for neuroprotection. Prog Neurobiol. 115:157–188. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Tang C, Wang C, Zhang Y, Xue L, Li Y, Ju C and Zhang C: Recognition, intervention, and monitoring of neutrophils in acute ischemic stroke. Nano Lett. 19:4470–4477. 2019. View Article : Google Scholar : PubMed/NCBI

14 

Dhanesha N, Patel RB, Doddapattar P, Ghatge M, Flora GD, Jain M, Thedens D, Olalde H, Kumskova M, Leira EC and Chauhan AK: PKM2 promotes neutrophil activation and cerebral thromboinflammation: Therapeutic implications for ischemic stroke. Blood. 139:1234–1245. 2022. View Article : Google Scholar : PubMed/NCBI

15 

Shi K, Tian DC, Li ZG, Ducruet AF, Lawton MT and Shi FD: Global brain inflammation in stroke. Lancet Neurol. 18:1058–1066. 2019. View Article : Google Scholar : PubMed/NCBI

16 

Iadecola C, Buckwalter MS and Anrather J: Immune responses to stroke: Mechanisms, modulation, and therapeutic potential. J Clin Invest. 130:2777–2788. 2020. View Article : Google Scholar : PubMed/NCBI

17 

Wang Q, Tang XN and Yenari MA: The inflammatory response in stroke. J Neuroimmunol. 184:53–68. 2007. View Article : Google Scholar : PubMed/NCBI

18 

Jayaraj RL, Azimullah S, Beiram R, Jalal FY and Rosenberg GA: Neuroinflammation: Friend and foe for ischemic stroke. J Neuroinflammation. 16:1422019. View Article : Google Scholar : PubMed/NCBI

19 

Lu D, Chen WQ, Wang YP, Duan WY, Guo L, Wang L, Liu L, Xu AD and Wang YJ: Scientific Statements on Brain Cytoprotection in Ischemic Stroke—A Scientific Statement from the Chinese Stroke Association. Chin J Stroke. 19:938–55. 2024.(In Chinese).

20 

Tanaka T and Kishimoto T: The biology and medical implications of interleukin-6. Cancer Immunol Res. 2:288–294. 2014. View Article : Google Scholar : PubMed/NCBI

21 

Taher MY, Davies DM and Maher J: The role of the interleukin (IL)-6/IL-6 receptor axis in cancer. Biochem Soc Trans. 46:1449–1462. 2018. View Article : Google Scholar : PubMed/NCBI

22 

Scheller J, Chalaris A, Schmidt-Arras D and Rose-John S: The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta. 1813:878–888. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Montgomery A, Tam F, Gursche C, Cheneval C, Besler K, Enns W, Manku S, Rey K, Hanson PJ, Rose-John S, et al: Overlapping and distinct biological effects of IL-6 classic and trans-signaling in vascular endothelial cells. Am J Physiol Cell Physiol. 320:C554–C565. 2021. View Article : Google Scholar : PubMed/NCBI

24 

Mihara M, Hashizume M, Yoshida H, Suzuki M and Shiina M: IL-6/IL-6 receptor system and its role in physiological and pathological conditions. Clin Sci (Lond). 122:143–159. 2012. View Article : Google Scholar : PubMed/NCBI

25 

Heo TH, Wahler J and Suh N: Potential therapeutic implications of IL-6/IL-6R/gp130-targeting agents in breast cancer. Oncotarget. 7:15460–15473. 2016. View Article : Google Scholar : PubMed/NCBI

26 

März P, Cheng JG, Gadient RA, Patterson PH, Stoyan T, Otten U and Rose-John S: Sympathetic neurons can produce and respond to interleukin 6. Proc Natl Acad Sci USA. 95:3251–3256. 1998. View Article : Google Scholar : PubMed/NCBI

27 

Heink S, Yogev N, Garbers C, Herwerth M, Aly L, Gasperi C, Husterer V, Croxford AL, Möller-Hackbarth K, Bartsch HS, et al: Trans-presentation of IL-6 by dendritic cells is required for the priming of pathogenic T(H)17 cells. Nat Immunol. 18:74–85. 2017. View Article : Google Scholar : PubMed/NCBI

28 

Gu Y, He M, Zhou X, Liu J, Hou N, Bin T, Zhang Y, Li T and Chen J: Endogenous IL-6 of mesenchymal stem cell improves behavioral outcome of hypoxic-ischemic brain damage neonatal rats by supressing apoptosis in astrocyte. Sci Rep. 6:185872016. View Article : Google Scholar : PubMed/NCBI

29 

Zhu H, Hu S, Li Y, Sun Y, Xiong X, Hu X, Chen J and Qiu S: Interleukins and ischemic stroke. Front Immunol. 13:8284472022. View Article : Google Scholar : PubMed/NCBI

30 

Pacinella G, Ciaccio AM, Casuccio A, Daidone M, Pecoraro R, Di Bona D, Del Cuore A, Puleo MG, Di Raimondo D, Di Chiara T, et al: Genetic polymorphisms and cytokine levels in ischemic stroke: Associations with subtypes and prognosis. Expert Rev Clin Immunol. 21:961–976. 2025. View Article : Google Scholar : PubMed/NCBI

31 

Huang X, Zhang M, Wang J and Hu F: Association between interleukin-6 levels and stroke: A systematic review and meta-analysis. J Int Med Res. 52:30006052412746262024. View Article : Google Scholar : PubMed/NCBI

32 

Sanderson TH, Reynolds CA, Kumar R, Przyklenk K and Hüttemann M: Molecular mechanisms of ischemia-reperfusion injury in brain: Pivotal role of the mitochondrial membrane potential in reactive oxygen species generation. Mol Neurobiol. 47:9–23. 2013. View Article : Google Scholar : PubMed/NCBI

33 

Shirley R, Ord EN and Work LM: Oxidative stress and the use of antioxidants in stroke. Antioxidants (Basel). 3:472–501. 2014. View Article : Google Scholar : PubMed/NCBI

34 

Dong X, Wu D, Zhang Y, Jia L, Pan X, Sun J and Pan LL: Cathelicidin modulates vascular smooth muscle cell phenotypic switching through ROS/IL-6 pathway. Antioxidants (Basel). 9:4912020. View Article : Google Scholar : PubMed/NCBI

35 

Yan M, Sun Z, Zhang S, Yang G, Jiang X, Wang G, Li R, Wang Q and Tian X: SOCS modulates JAK-STAT pathway as a novel target to mediate the occurrence of neuroinflammation: Molecular details and treatment options. Brain Res Bull. 213:1109882024. View Article : Google Scholar : PubMed/NCBI

36 

Zhang SR, Li CT, Yang Y and Zhang LH: Oxidative stress, inflammation and autophagy in cerebral ischemic injury: mechanisms and therapeutic strategies. Chin J Pharmacol Toxicol. 32:651–660. 2018.(In Chinese).

37 

Kang S and Kishimoto T: Interplay between interleukin-6 signaling and the vascular endothelium in cytokine storms. Exp Mol Med. 53:1116–1123. 2021. View Article : Google Scholar : PubMed/NCBI

38 

Henein MY, Vancheri S, Longo G and Vancheri F: The role of inflammation in cardiovascular disease. Int J Mol Sci. 23:129062022. View Article : Google Scholar : PubMed/NCBI

39 

Webb CE, Vautrinot J and Hers I: IL-6 as a mediator of platelet hyper-responsiveness. Cells. 14:7662025. View Article : Google Scholar : PubMed/NCBI

40 

Zhang W, Tian T, Gong SX, Huang WQ, Zhou QY, Wang AP and Tian Y: Microglia-associated neuroinflammation is a potential therapeutic target for ischemic stroke. Neural Regen Res. 16:6–11. 2021. View Article : Google Scholar : PubMed/NCBI

41 

Purroy F, Farré-Rodriguez J, Mauri-Capdevila G, Vicente-Pascual M and Farré J: Basal IL-6 and S100b levels are associated with infarct volume. Acta Neurol Scand. 144:517–523. 2021. View Article : Google Scholar : PubMed/NCBI

42 

Ohta M, Kihara T, Toriuchi K, Aoki H, Iwaki S, Kakita H, Yamada Y and Aoyama M: IL-6 promotes cell adhesion in human endothelial cells via microRNA-126-3p suppression. Exp Cell Res. 393:1120942020. View Article : Google Scholar : PubMed/NCBI

43 

Mo J, Chen Z, Wang M, Cheng A, Li J, Pan Y, Jiang Y, Jing J, Wang Y, Pu Y and Li Z: Association between interleukin-6 and multiple acute infarctions in symptomatic intracranial atherosclerotic disease. Curr Neurovasc Res. 21:292–299. 2024. View Article : Google Scholar : PubMed/NCBI

44 

Yang X, Liao KH, Deng IB and Zhang LC: Knockdown of interleukin-6 plays a neuroprotective role against hypoxia-ischemia in neonatal rats via inhibition of caspase 3 and Bcl-2-associated X protein signaling pathway. Ibrain. 8:413–428. 2022. View Article : Google Scholar : PubMed/NCBI

45 

Zhan L, Mu Z, Jiang H, Zhang S, Pang Y, Jin H, Chen J, Jia C and Guo H: MiR-21-5p protects against ischemic stroke by targeting IL-6R. Ann Transl Med. 11:1012023. View Article : Google Scholar : PubMed/NCBI

46 

Radak D, Resanovic I and Isenovic ER: Changes in hypothalamus-pituitary-adrenal axis following transient ischemic attack. Angiology. 65:723–732. 2014. View Article : Google Scholar : PubMed/NCBI

47 

Crofford LJ, Kalogeras KT, Mastorakos G, Magiakou MA, Wells J, Kanik KS, Gold PW, Chrousos GP and Wilder RL: Circadian relationships between interleukin (IL)-6 and hypothalamic-pituitary-adrenal axis hormones: Failure of IL-6 to cause sustained hypercortisolism in patients with early untreated rheumatoid arthritis. J Clin Endocrinol Metab. 82:1279–1283. 1997. View Article : Google Scholar : PubMed/NCBI

48 

Hassamal S: Chronic stress, neuroinflammation, and depression: An overview of pathophysiological mechanisms and emerging anti-inflammatories. Front Psychiatry. 14:11309892023. View Article : Google Scholar : PubMed/NCBI

49 

Roy M, Collier B and Roy A: Hypothalamic-pituitary-adrenal axis dysregulation among diabetic outpatients. Psychiatry Res. 31:31–37. 1990. View Article : Google Scholar : PubMed/NCBI

50 

Kim S, Park ES, Chen PR and Kim E: Dysregulated hypothalamic-pituitary-adrenal axis is associated with increased inflammation and worse outcomes after ischemic stroke in diabetic mice. Front Immunol. 13:8648582022. View Article : Google Scholar : PubMed/NCBI

51 

Kamtchum-Tatuene J, Saba L, Heldner MR, Poorthuis MHF, de Borst GJ, Rundek T, Kakkos SK, Chaturvedi S, Topakian R, Polak JF, et al: Interleukin-6 predicts carotid plaque severity, vulnerability, and progression. Circ Res. 131:e22–e33. 2022. View Article : Google Scholar : PubMed/NCBI

52 

Mehta NN, deGoma E and Shapiro MD: IL-6 and cardiovascular risk: A narrative review. Curr Atheroscler Rep. 27:122024. View Article : Google Scholar : PubMed/NCBI

53 

Lundin JI, Peters U, Hu Y, Ammous F, Benjamin EJ, Bis JC, Brody JA, Cushman M, Fuller H, Gignoux C, et al: Epigenetic mechanisms underlying variation of IL-6, a well-established inflammation biomarker and risk factor for cardiovascular disease. Atherosclerosis. 407:1202192025. View Article : Google Scholar : PubMed/NCBI

54 

Kitagawa K, Toi S, Yoshizawa H, Sato Y and Todo K: Association between serum levels of interleukin-6 and stroke, cardiovascular events, and Alzheimer's disease dementia. J Atheroscler Thromb. 32:1390–1399. 2025. View Article : Google Scholar : PubMed/NCBI

55 

Jenny NS, Callas PW, Judd SE, McClure LA, Kissela B, Zakai NA and Cushman M: Inflammatory cytokines and ischemic stroke risk: The REGARDS cohort. Neurology. 92:e2375–e2384. 2019. View Article : Google Scholar : PubMed/NCBI

56 

Papadopoulos A, Palaiopanos K, Björkbacka H, Peters A, de Lemos JA, Seshadri S, Dichgans M and Georgakis MK: Circulating interleukin-6 levels and incident ischemic stroke: A systematic review and meta-analysis of prospective studies. Neurology. 98:e1002–e1012. 2022. View Article : Google Scholar : PubMed/NCBI

57 

Jiang Y and Fan T: IL-6 and stroke recurrence in ischemic stroke. Biomark Med. 18:739–747. 2024. View Article : Google Scholar : PubMed/NCBI

58 

Xu J, Mo J, Zhang X, Chen Z, Pan Y, Yan H, Meng X and Wang Y: Nontraditional risk factors for residual recurrence risk in patients with ischemic stroke of different etiologies. Cerebrovasc Dis. 51:630–638. 2022. View Article : Google Scholar : PubMed/NCBI

59 

Li J, Lin J, Pan Y, Wang M, Meng X, Li H, Wang Y, Zhao X, Qin H, Liu L, et al: Interleukin-6 and YKL-40 predicted recurrent stroke after ischemic stroke or TIA: analysis of 6 inflammation biomarkers in a prospective cohort study. J Neuroinflammation. 19:1312022. View Article : Google Scholar : PubMed/NCBI

60 

McCabe JJ, Harris K, Walsh C, Gorey S, Arnold M, De Marchis GM, Hervella P, Iglesias-Rey R, Jern C, Katan M, et al: Interleukin-6, C-reactive protein, and vascular recurrence after stroke with and without atherosclerosis. Stroke. 56:2588–2596. 2025. View Article : Google Scholar : PubMed/NCBI

61 

Georgakis MK, Malik R, Gill D, Franceschini N, Sudlow CLM and Dichgans M; INVENT Consortium, CHARGE Inflammation Working Group, : Interleukin-6 signaling effects on ischemic stroke and other cardiovascular outcomes: A mendelian randomization study. Circ Genom Precis Med. 13:e0028722020. View Article : Google Scholar : PubMed/NCBI

62 

Zhang L, Omarov M, Xu L, deGoma E, Natarajan P and Georgakis MK: IL6 genetic perturbation mimicking IL-6 inhibition is associated with lower cardiometabolic risk. Nat Cardiovasc Res. 4:1172–1186. 2025. View Article : Google Scholar : PubMed/NCBI

63 

Cui JJ, Zhang CZ, Zhu B, Xu ZP and Liu YY: Serum miR-21-5p, IL-6, and IL-8 Expression Levels and Predictive Model Construction in Patients with Cerebral Infarction. Chin J Gerontology. 43:4103–4106. 2023.(In Chinese).

64 

Kowalski RG, Ledreux A, Violette JE, Paustian W, Sillau S, Thompson JA, Neumann RT, Ornelas D, Monte AA, Dylla L, et al: Circulating interleukin-6 levels and timing of acute ischemic stroke onset. Ann Clin Transl Neurol. 12:1926–1931. 2025. View Article : Google Scholar : PubMed/NCBI

65 

Su JH, Luo MY, Liang N, Gong SX, Chen W, Huang WQ, Tian Y and Wang AP: Interleukin-6: A novel target for cardio-cerebrovascular diseases. Front Pharmacol. 12:7450612021. View Article : Google Scholar : PubMed/NCBI

66 

Mosarrezaii A, Amiri-Nikpour MR, Mehryar HR, Choobi Anzali B, Nourooz-Zadeh S, Babaei S and Farrokhi H: Investigating the relationship between interleukin-6 serum levels and outcome in acute ischemic CVA. Brain Behav. 10:e016682020. View Article : Google Scholar : PubMed/NCBI

67 

Alfieri DF, Lehmann MF, Flauzino T, de Araújo MCM, Pivoto N, Tirolla RM, Simão ANC, Maes M and Reiche EMV: Immune-inflammatory, metabolic, oxidative, and nitrosative stress biomarkers predict acute ischemic stroke and short-term outcome. Neurotox Res. 38:330–343. 2020. View Article : Google Scholar : PubMed/NCBI

68 

Li X, Lin S, Chen X, Huang W, Li Q, Zhang H, Chen X, Yang S, Jin K and Shao B: The prognostic value of serum cytokines in patients with acute ischemic stroke. Aging Dis. 10:544–556. 2019. View Article : Google Scholar : PubMed/NCBI

69 

Jia WL, Jiang YY, Jiang Y, Meng X, Li H, Zhao XQ, Wang YL, Wang YJ, Gu HQ and Li ZX: Associations between admission levels of multiple biomarkers and subsequent worse outcomes in acute ischemic stroke patients. J Cereb Blood Flow Metab. 44:742–756. 2024. View Article : Google Scholar : PubMed/NCBI

70 

Gu HQ, Yang KX, Li JJ, Lin JX, Jing J, Xiong YY, Zhao XQ, Wang YL, Liu LP, Meng X, et al: Mediation effect of stroke recurrence in the association between post-stroke interleukin-6 and functional disability. CNS Neurosci Ther. 29:3579–3587. 2023. View Article : Google Scholar : PubMed/NCBI

71 

Dargazanli C, Blaquière M, Moynier M, de Bock F, Labreuche J, Ter Schiphorst A, Derraz I, Radu RA, Gascou G, Lefevre PH, et al: Inflammation biomarkers in the intracranial blood are associated with outcome in patients with ischemic stroke. J Neurointerv Surg. 17:159–166. 2025. View Article : Google Scholar : PubMed/NCBI

72 

Pawluk H, Kołodziejska R, Grześk G, Kozakiewicz M, Woźniak A, Pawluk M, Kosinska A, Grześk M, Wojtasik J and Kozera G: Selected mediators of inflammation in patients with acute ischemic stroke. Int J Mol Sci. 23:106142022. View Article : Google Scholar : PubMed/NCBI

73 

Hervella P, Rodríguez-Castro E, Rodríguez-Yáñez M, Arias S, Santamaría-Cadavid M, López-Dequidt I, Estany-Gestal A, Maqueda E, López-Loureiro I, Sobrino T, et al: Intra- and extra-hospital improvement in ischemic stroke patients: Influence of reperfusion therapy and molecular mechanisms. Sci Rep. 10:35132020. View Article : Google Scholar : PubMed/NCBI

74 

Băcilă CI, Vlădoiu MG, Văleanu M, Moga DF and Pumnea PM: The role of IL-6 and TNF-alpha biomarkers in predicting disability outcomes in acute ischemic stroke patients. Life Basel). 15:472025. View Article : Google Scholar : PubMed/NCBI

75 

Yi L, Li ZX, Jiang YY, Jiang Y, Meng X, Li H, Zhao XQ, Wang YL, Liu LP, Wang YJ and Gu HQ: Inflammatory marker profiles and in-hospital neurological deterioration in patients with acute minor ischemic stroke. CNS Neurosci Ther. 30:e146482024. View Article : Google Scholar : PubMed/NCBI

76 

Sabir Rashid A, Huang-Link Y, Johnsson M, Wetterhäll S and Gauffin H: Predictors of early neurological deterioration and functional outcome in acute ischemic stroke: The importance of large artery disease, hyperglycemia and inflammatory blood biomarkers. Neuropsychiatr Dis Treat. 18:1993–2002. 2022. View Article : Google Scholar : PubMed/NCBI

77 

Deng QW, Huang S, Li S, Zhai Q, Zhang Q, Wang ZJ, Chen WX, Sun H, Lu M and Zhou J: Inflammatory factors as potential markers of early neurological deterioration in acute ischemic stroke patients receiving endovascular therapy-the AISRNA study. J Inflamm Res. 14:4399–4407. 2021. View Article : Google Scholar : PubMed/NCBI

78 

Grebenciucova E and VanHaerents S: Interleukin 6: At the interface of human health and disease. Front Immunol. 14:12555332023. View Article : Google Scholar : PubMed/NCBI

79 

Hall C, Nguyen DT, Mendoza K, Tan C and Chauhan A: Inhibition of IL-6 trans-signaling promotes post-stroke functional recovery in a sex and dose-dependent manner. J Neuroinflammation. 22:522025. View Article : Google Scholar : PubMed/NCBI

80 

Hudobenko J, Chauhan A and McCullough L: Abstract 128: Amelioration of ischemic stroke damage through inhibition of interleukin-6 signaling with tocilizumab requires sex specific dosing. Stroke. 50 (Suppl 1):A1282019. View Article : Google Scholar

81 

Schuett H, Oestreich R, Waetzig GH, Annema W, Luchtefeld M, Hillmer A, Bavendiek U, von Felden J, Divchev D, Kempf T, et al: Transsignaling of interleukin-6 crucially contributes to atherosclerosis in mice. Arterioscler Thromb Vasc Biol. 32:281–290. 2012. View Article : Google Scholar : PubMed/NCBI

82 

Ministrini S, Liberale L, Puspitasari YM, Han J, Kirmes K, Unkelbach LP, Tirandi A, Niederberger R, Bengs S, Beer JH, et al: Direct interleukin-6 inhibition blunts arterial thrombosis by reducing collagen-mediated platelet activation. Arterioscler Thromb Vasc Biol. 45:1432–1439. 2025. View Article : Google Scholar : PubMed/NCBI

83 

Chu X, Ma Z, Liu Y, Sun J, Wang N, Li C, Feng X, Li J, Wang B, Zhou C, et al: IRIS, a randomised, double-blind, placebo-controlled trial of interleukin-6 receptor inhibition undergoing endovascular treatment in acute anterior circulation ischaemic stroke: Study rationale and design. Stroke Vasc Neurol. 10:514–519. 2025. View Article : Google Scholar : PubMed/NCBI

84 

Huse C, Anstensrud AK, Michelsen AE, Ueland T, Broch K, Woxholt S, Yang K, Sharma K, Tøllefsen IM, Bendz B, et al: Interleukin-6 inhibition in ST-elevation myocardial infarction: Immune cell profile in the randomised ASSAIL-MI trial. EBioMedicine. 80:1040132022. View Article : Google Scholar : PubMed/NCBI

85 

Ridker PM, Devalaraja M, Baeres FMM, Engelmann MDM, Hovingh GK, Ivkovic M, Lo L, Kling D, Pergola P, Raj D, et al: IL-6 inhibition with ziltivekimab in patients at high atherosclerotic risk (RESCUE): A double-blind, randomised, placebo-controlled, phase 2 trial. Lancet. 397:2060–2069. 2021. View Article : Google Scholar : PubMed/NCBI

86 

GlobeNewswire, . Tourmaline Bio Announces Positive Topline Results from the Ongoing Phase 2 TRANQUILITY Trial Evaluating Pacibekitug in Patients with Elevated High-Sensitivity C-reactive Protein and Chronic Kidney Disease. Tourmaline Inc.; https://www.globenewswire.com/news-release/2025/05/20/3084742/0/en/Tourmaline-Bio-Announces-Positive-Topline-Results-from-the-Ongoing-Phase-2-TRANQUILITY-Trial-Evaluating-Pacibekitug-in-Patients-with-Elevated-High-Sensitivity-C-reactive-Protein-an.htmlAugust 7–2025

87 

Ridker PM: From RESCUE to ZEUS: will interleukin-6 inhibition with ziltivekimab prove effective for cardiovascular event reduction? Cardiovasc Res. 117:e138–e140. 2021. View Article : Google Scholar : PubMed/NCBI

88 

Ridker PM and Rane M: Interleukin-6 signaling and anti-interleukin-6 therapeutics in cardiovascular disease. Circ Res. 128:1728–1746. 2021. View Article : Google Scholar : PubMed/NCBI

89 

Rose-John S, Jenkins BJ, Garbers C, Moll JM and Scheller J: Targeting IL-6 trans-signalling: Past, present and future prospects. Nat Rev Immunol. 23:666–681. 2023. View Article : Google Scholar : PubMed/NCBI

90 

Jostock T, Müllberg J, Ozbek S, Atreya R, Blinn G, Voltz N, Fischer M, Neurath MF and Rose-John S: Soluble gp130 is the natural inhibitor of soluble interleukin-6 receptor transsignaling responses. Eur J Biochem. 268:160–167. 2001. View Article : Google Scholar : PubMed/NCBI

91 

Weiss A and Ding Y: Beyond reperfusion: Adjunctive therapies targeting inflammation, edema, and blood-brain barrier dysfunction in ischemic stroke. Cerebrovasc Dis. 1–10. 2025.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI

92 

Acalovschi D, Wiest T, Hartmann M, Farahmi M, Mansmann U, Auffarth GU, Grau AJ, Green FR, Grond-Ginsbach C and Schwaninger M: Multiple levels of regulation of the interleukin-6 system in stroke. Stroke. 34:1864–1869. 2003. View Article : Google Scholar : PubMed/NCBI

93 

Ziegler L, Wallén H, Aspberg S, de Faire U and Gigante B: IL6 trans-signaling associates with ischemic stroke but not with atrial fibrillation. BMC Neurol. 21:3062021. View Article : Google Scholar : PubMed/NCBI

94 

Ridker PM, Libby P, MacFadyen JG, Thuren T, Ballantyne C, Fonseca F, Koenig W, Shimokawa H, Everett BM and Glynn RJ: Modulation of the interleukin-6 signalling pathway and incidence rates of atherosclerotic events and all-cause mortality: Analyses from the canakinumab anti-inflammatory thrombosis outcomes study (CANTOS). Eur Heart J. 39:3499–3507. 2018. View Article : Google Scholar : PubMed/NCBI

95 

Zhu S, Pan W, Yao Y and Shi K: The efficacy of colchicine compared to placebo for preventing ischemic stroke among individuals with established atherosclerotic cardiovascular diseases: A systematic review and meta-analysis. Scand Cardiovasc J. 59:24411122025. View Article : Google Scholar : PubMed/NCBI

96 

Fiolet ATL, Poorthuis MHF, Opstal TSJ, Amarenco P, Boczar KE, Buysschaert I, Budgeon C, Chan NC, Cornel JH, Jolly SS, et al: Colchicine for secondary prevention of ischaemic stroke and atherosclerotic events: A meta-analysis of randomised trials. EClinicalMedicine. 76:1028352024. View Article : Google Scholar : PubMed/NCBI

97 

Shi K, Zou M, Jia DM, Shi S, Yang X, Liu Q, Dong JF, Sheth KN, Wang X and Shi FD: tPA mobilizes immune cells that exacerbate hemorrhagic transformation in stroke. Circ Res. 128:62–75. 2021. View Article : Google Scholar : PubMed/NCBI

98 

Wang H, Tian X, Liao Z, Yue X, Sun L, Li X, Zou M and Ding J: Inflammatory biomarkers may be associated with poor outcomes after mechanical thrombectomy. Thromb J. 22:582024. View Article : Google Scholar : PubMed/NCBI

99 

Jafari M, Katlowitz K, De la Garza C, Sellers A, Moore S, Hall H, Desai A, Singh V and Damani R: Impact of systemic inflammatory response syndrome on acute ischemic stroke patients treated with mechanical thrombectomy. J Neurol Sci. 430:1199882021. View Article : Google Scholar : PubMed/NCBI

100 

Jia Y, Zhang K, Shi M, Guo D, Yang P, Bu X, Chen J, Wang A, Xu T, He J, et al: Associations of rheumatoid factor, rheumatoid arthritis, and interleukin-6 inhibitor with the prognosis of ischemic stroke: A prospective multicenter cohort study and mendelian randomization analysis. Transl Stroke Res. 15:750–760. 2024. View Article : Google Scholar : PubMed/NCBI

101 

Scheller J and Rose-John S: The interleukin 6 pathway and atherosclerosis. Lancet. 380:3382012. View Article : Google Scholar : PubMed/NCBI

102 

Zhang M, Bai Y, Wang Y, Cui H, Tang M, Wang L, Wang X and Gu D: Cumulative evidence for associations between genetic variants in interleukin 6 receptor gene and human diseases and phenotypes. Front Immunol. 13:8607032022. View Article : Google Scholar : PubMed/NCBI

103 

Georgakis MK, Malik R, Li X, Gill D, Levin MG, Vy HMT, Judy R, Ritchie M, Verma SS; Regeneron Genetics Center, ; et al: Genetically downregulated interleukin-6 signaling is associated with a favorable cardiometabolic profile: A phenome-wide association study. Circulation. 143:1177–1780. 2021. View Article : Google Scholar : PubMed/NCBI

104 

Said EA, Al-Reesi I, Al-Shizawi N, Jaju S, Al-Balushi MS, Koh CY, Al-Jabri AA and Jeyaseelan L: Defining IL-6 levels in healthy individuals: A meta-analysis. J Med Virol. 93:3915–3924. 2021. View Article : Google Scholar : PubMed/NCBI

105 

Docherty S, Harley R, McAuley JJ, Crowe LAN, Pedret C, Kirwan PD, Siebert S and Millar NL: The effect of exercise on cytokines: Implications for musculoskeletal health: A narrative review. BMC Sports Sci Med Rehabil. 14:52022. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wang X, Zhang X, Lin J and Lin P: Interleukin‑6 and ischemic stroke: From mechanisms to clinical prospects (Review). Mol Med Rep 33: 80, 2026.
APA
Wang, X., Zhang, X., Lin, J., & Lin, P. (2026). Interleukin‑6 and ischemic stroke: From mechanisms to clinical prospects (Review). Molecular Medicine Reports, 33, 80. https://doi.org/10.3892/mmr.2026.13790
MLA
Wang, X., Zhang, X., Lin, J., Lin, P."Interleukin‑6 and ischemic stroke: From mechanisms to clinical prospects (Review)". Molecular Medicine Reports 33.3 (2026): 80.
Chicago
Wang, X., Zhang, X., Lin, J., Lin, P."Interleukin‑6 and ischemic stroke: From mechanisms to clinical prospects (Review)". Molecular Medicine Reports 33, no. 3 (2026): 80. https://doi.org/10.3892/mmr.2026.13790
Copy and paste a formatted citation
x
Spandidos Publications style
Wang X, Zhang X, Lin J and Lin P: Interleukin‑6 and ischemic stroke: From mechanisms to clinical prospects (Review). Mol Med Rep 33: 80, 2026.
APA
Wang, X., Zhang, X., Lin, J., & Lin, P. (2026). Interleukin‑6 and ischemic stroke: From mechanisms to clinical prospects (Review). Molecular Medicine Reports, 33, 80. https://doi.org/10.3892/mmr.2026.13790
MLA
Wang, X., Zhang, X., Lin, J., Lin, P."Interleukin‑6 and ischemic stroke: From mechanisms to clinical prospects (Review)". Molecular Medicine Reports 33.3 (2026): 80.
Chicago
Wang, X., Zhang, X., Lin, J., Lin, P."Interleukin‑6 and ischemic stroke: From mechanisms to clinical prospects (Review)". Molecular Medicine Reports 33, no. 3 (2026): 80. https://doi.org/10.3892/mmr.2026.13790
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team