DYNAMICS OF THE PRO-INFLAMMATORY CYTOKINE RESPONSE IN RATS UNDER CONDITIONS OF EXPERIMENTAL ACUTE PANCREATITIS
DOI:
https://doi.org/10.11603/mcch.2410-681X.2026.i3.16598Keywords:
acute pancreatitis; pro-inflammatory cytokines; TNF-α, IL-1β, IL-6Abstract
Introduction. Acute pancreatitis is accompanied not only by local pancreatic injury but also by early activation of the systemic immune-inflammatory response. Assessment of the temporal dynamics of pro-inflammatory cytokines may clarify the initial mechanisms of the inflammatory cascade and the development of systemic inflammation. The aim of the study – to investigate changes in serum TNF-α, IL-1β and IL-6 levels in rats with experimental acute pancreatitis. Research Methods. The study was performed on male Wistar rats weighing 180–220 g. Animals were divided into a control group (n = 10) and an experimental group (n = 38) with induced acute pancreatitis. The model was reproduced by intraperitoneal administration of a 20 % L-arginine solution at a total dose of 5 g/kg body weight, with a one-hour interval between injections. Blood sampling was carried out 1, 6, 12 and 24 h after L-arginine administration. Serum TNF-α, IL-1β and IL-6 concentrations were determined by enzyme-linked immunosorbent assay. Statistical analysis was performed with significance accepted at p < 0,05. Results and Discussion. Experimental acute pancreatitis was associated with a significant increase in TNF-α, IL-1β and IL-6 at all observation time points compared with control values. TNF-α exceeded the control level by 1,41 times after 1 h, 3,47 times after 6 h, 5,69 times after 12 h and 8,38 times after 24 h. The most pronounced changes were observed for IL-1β, whose level increased by 3,32, 19,74, 33,19 and 47,68 times, respectively. IL-6 also increased significantly throughout the experiment, exceeding the control level by 1,44 times after 1 h, 2,46 times after 6 h, 3,12 times after 12 h and 3,97 times after 24 h. This pattern suggests progressive intensification of the pro-inflammatory cascade during the first day after pancreatic damage. Conclusions. Experimental acute pancreatitis is accompanied by an early and persistent increase in TNF-α, IL-1β and IL-6 in rat serum. The predominant rise in IL-1β may indicate its particular role in the development of the pro-inflammatory cytokine response at the early stages of acute pancreatitis.
References
1. Glaubitz, J., Asgarbeik, S., Lange, R., Mazloum, H., Elsheikh, H., Weiss, F. U., & Sendler, M. (2023). Immune response mechanisms in acute and chronic pancreatitis: Strategies for therapeutic intervention. Frontiers in Immunology, 14, 1279539. https://doi.org/10.3389/fimmu.2023.1279539 DOI: https://doi.org/10.3389/fimmu.2023.1279539
2. Lee, P. J., & Papachristou, G. I. (2019). New insights into acute pancreatitis. Nature Reviews Gastroenterology & Hepatology, 16, 479–496. https://doi.org/10.1038/s41575-019-0158-2 DOI: https://doi.org/10.1038/s41575-019-0158-2
3. Huang, D. Y., Li, Q., Shi, C. Y., Hou, C. Q., Miao, Y., & Shen, H .B. (2020). Dexmedetomidine attenuates inflammation and pancreatic injury in a rat model of experimental severe acute pancreatitis via cholinergic anti-inflammatory pathway. Chinese Medical Journal, 133, 1073–1079. https://doi.org/10.1097/CM9.0000000000000766 DOI: https://doi.org/10.1097/CM9.0000000000000766
4. Eltahir, H. M., Elbadawy, H. M., Almikhlafi, M. A., Alalawi, A. M., Aldhafiri, A. J., Alahmadi, Y. M., … Abouzied, M. M. (2024). Sitagliptin ameliorates L-arginineinduced acute pancreatitis via modulating inflammatory cytokines expression and combating oxidative stress. Frontiers in Pharmacology, 15, 1389670. https://doi.org/10.3389/fphar.2024.1389670 DOI: https://doi.org/10.3389/fphar.2024.1389670
5. Berezniakov, V. I., Korzh, O. M., & Pavlov, S. B. (2021). Cytokines as mediators of the immune system and their role in the pathogenesis of community-acquired pneumonia. World of Medicine and Biology, 3 (77), 33–37. https://doi.org/10.26724/2079-8334-2021-3-77-33-37 [in Ukrainian]. DOI: https://doi.org/10.26724/2079-8334-2021-3-77-33-37
6. Makhovsky, V. P., Osinchuk, R. D., & Marushchak, M. I. (2015). Role of cytokines in the development of acute lung injury. Journal of Education, Health and Sport, 5 (1), 133–138. https://doi.org/10.5281/zenodo.14193
7. Shapoval, S. D., Savon, I. L., Trybushnyi, O. V., Maksymova, O. O., & Sofilkanych, M.M. (2020). Cytokine status in patients with sepsis. Zaporizhzhia Medical Journal, 4 (121), 515–519. https://doi.org/10.14739/2310-1210.2020.4.208375 [in Ukrainian]. DOI: https://doi.org/10.14739/2310-1210.2020.4.208375
8. Liang, X. Y., Jia, T. X., & Zhang, M. (2021). Intestinal bacterial overgrowth in the early stage of severe acute pancreatitis is associated with acute respiratory distress syndrome. World Journal of Gastroenterology, 27 (15), 1643–1654. https://doi.org/10.3748/wjg.v27.i15.1643 DOI: https://doi.org/10.3748/wjg.v27.i15.1643
9. Zhou, Y., Zhao, L., Mei, F., Hong, Y., Xia, H., Zuo, T., … Wang, W. (2018). Macrophage migration inhibitory factor antagonist (S,R)3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester attenuates inflammation and lung injury in rats with acute pancreatitis in pregnancy. Molecular Medicine Reports, 17, 6576–6584. https://doi.org/10.3892/mmr.2018.8672 DOI: https://doi.org/10.3892/mmr.2018.8672
10. Kınacı, E., Sevinc, M. M., Demir, A., Erdogan, E., Ahlatci, F. A., & Idiz, U. O. (2024). Changes in cytokines and chemokines in an acute pancreatitis model. Turkish Journal of Trauma & Emergency Surgery, 30 (4), 229–235. https://doi.org/10.14744/tjtes.2024.18049 DOI: https://doi.org/10.14744/tjtes.2024.18049
11. Zhou, R., Bu, W., Fan, Y., Du, Z., Zhang, J., Zhang, S., … Li, J. (2023). Dynamic changes in serum cytokine profile in rats with severe acute pancreatitis. Medicina, 59 (2), 321. https://doi.org/10.3390/medicina59020321 DOI: https://doi.org/10.3390/medicina59020321
12. Mizunuma, T., Kawamura, S., & Kishino, Y. (1984). Effects of injecting excess arginine on rat pancreas. The Journal of Nutrition, 114 (3), 467–471. https://doi.org/10.1093/jn/114.3.467 DOI: https://doi.org/10.1093/jn/114.3.467
13. Xu, H., Yue, H., Ge, H., & Wang, F. (2024). Vitamin B6 ameliorates acute pancreatitis by suppressing the caspase3 signaling pathway. BMC Gastroenterology, 24, 151. https://doi.org/10.1186/s12876-024-03248-1 DOI: https://doi.org/10.1186/s12876-024-03248-1
14. Yao, J., Lan, B., Ma, C., Liu, Y., Wu, X., Feng, K., … Wen, Q. (2023). RNA-sequencing approach for exploring the protective mechanisms of dexmedetomidine on pancreatic injury in severe acute pancreatitis. Frontiers in Pharmacology, 14, 1189486. https://doi.org/10.3389/fphar.2023.1189486 DOI: https://doi.org/10.3389/fphar.2023.1189486
15. Malheiro, F., Angelo-Dias, M., Lopes, T., Gregório Martins, C., & Borrego, L.M. (2024). Cytokine dynamics in acute pancreatitis: The quest for biomarkers from acute disease to disease resolution. Journal of Clinical Medicine, 13 (8), 2287. https://doi.org/10.3390/jcm13082287 DOI: https://doi.org/10.3390/jcm13082287
16. Kan, M. H., Yang, T., Fu, H. Q., Fan, L., Wu, Y., Terrando, N., & Wang, T.-L. (2016). Pyrrolidine dithiocarbamate prevents neuroinflammation and cognitive dysfunction after endotoxemia in rats. Frontiers in Aging Neuroscience, 8, Article 175. https://doi.org/10.3389/fnagi.2016.00175 DOI: https://doi.org/10.3389/fnagi.2016.00175
