ABSTRACT

INTRODUCTION. Despite significant experience in studying the role of cytokines in the regulation of the mechanisms of ischemia, verification of biomarkers of the severity of ischemic stroke currently remains insufficiently covered. In this connection, assessment of the immunological status of patients in the acute period of ischemic stroke is a promising research direction of modern angioneurology.

AIM. To evaluate the presence and dynamics of cytokines in the acute period of ischemic stroke in patients with mild and moderate severity of neurological deficit.

MATERIALS AND METHODS. 128 patients diagnosed with ischemic stroke were examined. Stroke severity was measured according to the National Institutes of Health Stroke Scale (NIHSS). Depending on the NIHSS score, patients were divided into two groups: group 1 – 60 patients with mild severity (NIHSS <5 points), group 2 – 68 patients with moderate severity (NIHSS - 5-15 points) of ischemic stroke. Immunological diagnostics included assessment of plasma concentrations of IL-1b, IL-16, IL-8, GM-CSF, TNFα and IFN-g on days 1 and 14 of hospitalization.

RESULTS. Assessment of serum cytokine concentrations at admission revealed a significant increase in the concentrations of IL-16 (p = 0.002), IL-6 (p = 0.026) and IFN-g (p = 0.021) in patients of group 2. On the day 14 of hospitalization, a significant (p < 0.0001) decrease in the concentrations of GM-CSF and IL-1b and an increase in the level of IFN-g was detected in patients of group 1; in patients of group 2 - a significant increase in GM-CSF concentrations  (p < 0.0001). A comparative analysis of cytokine levels on the day 14 of hospitalization revealed higher levels of IFN-g (p < 0.0001), GM-CSF (p < 0.0001), IL-6 (p = 0.0036), IL-16 (p < 0.0001) and IL-1b (p = 0.0002) in patients of group 2 compared with patients of group 1.

CONCLUSION. Concentrations of the cytokines IL-16, IL-6 and IFN-g were identified as indicators of the severity of ischemic stroke on the first day. The level and changes in the concentration of GM-CSF can be considered as a biomarker of the course of the acute period of ischemic stroke, regardless of the NIHSS indicator; a decrease in the concentration of IL-1b as a predictor of a favorable outcome, and an increase in IFN-g as an immunological indicator of the severity of atherothrombotic stroke. For a deeper understanding of the influence of identified immunological markers on the course and severity of ischemia, further prospective studies are needed to evaluate cytokines at different times from the development of  ischemic stroke in patients with varying severity of neurological deficit.

KEYWORDS: ischemic stroke, immunological status, stroke severity, cytokines

For citation: Tynterova A.M., Shusharina N.N. Dynamics of Immunological Parameters in Patients with Varying Severity of Ischemic Stroke in the Acute Period: Prospective Cohort Study. Comorbidity Neurology. 2025; 2 (1): 6-12. https://doi.org/10.62505/3034-185x-2025-2-1-6-12

*For correspondence: Anastasya M. Tynterova, Cand. Sci. (Med.), Senior Researcher, Baltic Center for Artificial Intelligence and Neurotechnology, Imannuel Kant Baltic Federal University, Kaliningrad, Russia. E-mail:  antynterova@mail.ru; ORCID: https://orcid.org/0000-0003-1743-4713

REFERENCES

1.Chernykh E.R., Shevela E.Ya., Morozov S.A., Ostanin A.A. Immunopathogenetic aspects of ischemic stroke. Medical Immunology. 2018; 20 (1): 19-34. https://doi.org/10.15789/1563-0625-2018-1-19-34 (In Russ.)

2. Iadecola C., Buckwalter M.S., Anrather J. Immune responses to stroke: mechanisms, modulation, and therapeutic potential. J Clin Invest. 2020 Jun 1; 130 (6): 2777-2788. https://doi.org/10.1172/JCI135530

3. Matys P., Mirończuk A., Starosz A., Grubczak K., Kochanowicz J., Kułakowska A., Kapica-Topczewska K. Expanding Role of Interleukin-1 Family Cytokines in Acute Ischemic Stroke. Int J Mol Sci. 2024; 25 (19): 10515. https://doi.org/10.3390/ijms251910515

4. Xue Y., Zeng X., Tu W.J., Zhao J. Tumor Necrosis Factor-α: The Next Marker of Stroke. Dis Markers. 2022; 2022: 2395269. https://doi.org/10.1155/2022/2395269

5. Theoret J.K., Jadavji N.M., Zhang M., Smith P.D. Granulocyte macrophage colony-stimulating factor treatment results in recovery of motor function after white matter damage in mice. Eur J Neurosci. 2016; 43 (1): 17-24. https://doi.org/10.1111/ejn.13105

6.Zurochka A.V., Zurochka V.A., Dobrynina M.A., Gritsenko V.A. Immunobiological properties of granulocytemacrophage colony-stimulating factor and synthetic peptides of his active center. Medical Immunology. 2021; 23 (5): 1031-1054. https://doi.org/10.15789/1563-0625-IPO-2216  (In Russ.)

7. Navarro-Sobrino M., Rosell A., Penalba A., Ribó M., Alvarez-Sabín J., Fernández-Cadenas I., Montaner J. Role of endogenous granulocyte-macrophage colony stimulating factor following stroke and relationship to neurological outcome. Curr Neurovasc Res. 2009; 6 (4): 246-51. https://doi.org/10.2174/156720209789630366

8.Dames C., Winek K., Beckers Y., Engel O., Meisel A., Meisel C. Immunomodulatory treatment with systemic GM-CSF augments pulmonary immune responses and improves neurological outcome after experimental stroke. J Neuroimmunol. 2018; 321: 144-149. https://doi.org/10.1016/j.jneuroim.2018.03.005

9.Huang X., Liu Y., Bai S., Peng L., Zhang B., Lu H. Granulocyte colony stimulating factor therapy for stroke: A pairwise meta-analysis of randomized controlled trial. PLoS One. 2017; 12(4): e0175774.  https://doi.org/10.1371/journal.pone.0175774

10.Kazmi S., Salehi-Pourmehr H., Sadigh-Eteghad S., Farhoudi M. The efficacy and safety of interleukin-1 receptor antagonist in stroke patients: A systematic review. J Clin Neurosci. 2024; 120: 120-128. https://doi.org/10.1016/j.jocn.2024.01.009

11. Maida C.D., Norrito R.L., Daidone M., Tuttolomondo A., Pinto A. Neuroinflammatory Mechanisms in Ischemic Stroke: Focus on Cardioembolic Stroke, Background, and Therapeutic Approaches. Int J Mol Sci. 2020; 21 (18): 6454. https://doi.org/10.3390/ijms21186454

12.Zhang D., Ren J., Luo Y., He Q., Zhao R., Chang J., Yang Y., Guo Z.N. T Cell Response in Ischemic Stroke: From Mechanisms to Translational Insights. Front Immunol. 2021; 12:707972. https://doi.org/10.3389/fimmu.2021.707972

13. Zhu H., Hu S., Li Y., Sun Y., Xiong X., Hu X., Chen J., Qiu S. Interleukins and Ischemic Stroke. Front Immunol. 2022; 13: 828447. https://doi.org/10.3389/fimmu.2022.828447

ADDITIONAL INFORMATION

Anastasya M. Tynterova, Cand. Sci. (Med.), Senior Researcher, Baltic Center for Artificial Intelligence and Neurotechnology, Imannuel Kant Baltic Federal University, Kaliningrad, Russia. E-mail: antynterova@mail.ru. ORCID: https://orcid.org/0000-0003-1743-4713

Natalia N. Shusharina, Cand. Sci. (Pedag.). Head of Development and Innovation Department, senior Researcher. Baltic Center for Artificial Intelligence and Neurotechnology, Imannuel Kant Baltic Federal University, Kaliningrad, Russia. E-mail: nnshusharina@gmail.com. ORCID: https://orcid.org/0000-0002-8848-6134

Author contributions. All authors confirm that their authorship complies with the international ICMJE criteria (all authors made a significant contribution to the development of the concept, the conduct of the study and the preparation of the article, read and approved the final version before publication). Special contributions: Tynterova A.M. – conceptualization, methodology, investigation, writing – review & editing; Shusharina N.N. – data curation, investigation, formal analysis, writing — original draft

Funding. This work was performed within the scope of the of the "Priority 2030" program and State assignment FZWM-2024-0013 (Immanuel Kant Baltic Federal University).

Disclosure. The authors declare no apparent or potential conflicts of interest related to the publication of this article.

Ethics Approval. The study was approved by the Independent Ethics Committee of the Independent Ethics Committee of the Center for Clinical Research of Imannuel Kant Baltic Federal University, (Kaliningrad, Russia) (Protocol № 2 of April 27, 2021).

Informed consent for publication. All patients, and if it is impossible to review and sign, persons responsible for the patients (relatives, social workers, etc.) on behalf of the patients undergoing examination and participating in this study, signed informed consent.

The content is available under the Creative Commons Attribution 4.0 License.

©2025. Anastasya M. Tynterova, Natalia N. Shusharina