Correlations between Serum Interleukin-4 with Pro- and Anti-inflammatory Markers in Type 1 and 2 Diabetes: A Comparative Study
Copyright (c) 2025 Zhian M.I. Dezayee (Author)

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
- Articles
- Submited: June 24, 2025
-
Published: August 20, 2025
Abstract
Background and objective: Interleukin-4 inhibits the secretion of many inflammatory cytokines and it acts as anti-inflammatory against insulinits that induced by autoimmunity in type-1 diabetes. This cross-sectional study aimed to determine the serum level IL-4 in patients with T1D and T2D, and to look into its relation to other pro-and anti- inflammatory cytokines and glycemic status.
Methods: Patients with a history of type-1 (T1D) (Group I, n=75) and type-2 (T2D) diabetes (Group II, n=75) were recruited from the Center of Diabetes in Erbil. Glycemic indices (included fasting serum glucose, insulin, glycated hemoglobin, c- peptide) and inflammatory-related cytokines (including highly sensitive C-reactive protein [hs-CRP], IL-1β, IL-4, IL-10, Interferon [INF-γ], and tumor necrosis factor [TNF-α]) were measured.
Results: Group II patients showed significant increase of hs-CRP, IL-10, and IL-4, while the serum levels of IL-1β and INF-γ were significantly reduced compared with Group I. Significant inverse correlations between IL-4 with each of the following markers; hs-CRP (r=-0.858), IL-1β(r=-0.890), INF-γ(r=-0.859), IL-10(-0.685), and TNF-α (r=-0.733) with predictive values ranged between 46.9% and 73.8% were observed in the Group II but not in the Group I. Non-significant correlation between IL-4 and glycemic indices were observed in Group I and II.
Conclusion: We conclude that determination of IL-4 can help to discriminate between autoimmune-from inflammatory markers that are associated with diabetes, and can serve as a predictor cytokine in T2D.
Metrics
References
- Hsieh, CS, Heimberger, AB, Gold, JS, O'Garra, A, Murphy, KM. Differential regulation of T helper phenotype development by interleukins 4 and 10 in an alpha beta T-cell-receptor transgenic system. Proc Natl Acad Sci USA. 1992; 89(13):6065–9.doi.org/10.1073/pnas.89.13.6065
- Szczepankiewicz D, Skrzypski M, Pruszyńska-Oszmałek E, Kołodziejski PA, Sassek M, Stefańska B, et al. Interleukin 4 affects lipid metabolism and the expression of pro-inflammatory factors in mature rat adipocytes. IMMUNOBIOLOGY. 2018; 223(11):677-83. doi.org/10.1016/j.imbio.2018.07.014
- Stafeev IS, Michurina SS, Podkuychenko NV, Vorotnikov AV, Menshikov MY, Parfyonova YV. Interleukin-4 restores insulin sensitivity in lipid- induced insulin-resistant adipocytes. BIOCHEMISTRY (MOSC). 2018; 83(5):498-506. doi.org/10.1134/S0006297918050036
- Mueller R, Krahl T, Sarvetnick N. Pancreatic expression of interleukin-4 abrogates insulitis and autoimmune diabetes in nonobese diabetic (NOD) mice. J Exp. Med. 1996; 184(3):1093–9. doi.org/10.1084/jem.184.3.1093
- teVelde AA, Huijbens RJ, Heije K, de Vries JE, Figdor CG. Interleukin-4 (IL-4) inhibits secretion of IL-1 beta, tumor necrosis factor alpha, and IL-6 by human monocyte. BLOOD. 1990; 76(7):1392–7. doi.org/10.1182/blood.V76.7.1392.1392
- Denis GV, Sebastiani P, Andrieu G, Tran AH, Strissel KJ, Lombardi FL, et al. Relationships among obesity, type 2 diabetes, and plasma cytokines in African American women. OBES (Silver Spring). 2017; 25(11):1916-20. doi.org/10.1002/oby.21943
- Bid HK, Konwar R, Agrawal CG, Banerjee M. Association of IL-4 and IL-1RN (receptor antagonist) gene variants and the risk of type 2 diabetes mellitus: A study in the north Indian population. Indian J Med Sci. 2008; 62(7):259–66.
- Pérez F, Oyarzún A, Carrasco E, Angel B, Albala C, Santos JL. Plasma levels of interleukin-1 beta, interleukin-2 and interleukin-4 in recently diagnosed type 1 diabetic children and their association with beta- pancreatic autoantibodies. Rev Med Chil. 2004;132(4):413-20. doi.org/10.4067/s0034-98872004000400002
- Pilla SJ, Maruthur NM, Schweitzer MA, Magnuson TH, Potter JJ, Clark JM, et al. The role of laboratory testing in differentiating type 1 diabetes from type 2 diabetes in patients undergoing bariatric surgery. Obes Surg. 2018; 28(1):25-30. doi.org/10.1007/s11695-017-2804-5
- Ziegler AG, Rewers M, Simell O, Simell T, Lempainen J, Steck A, et al. Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA. 2013; 309(23):2473–9. doi:10.1001/jama.2013.6285
- Raghav A, Ahmad J, Alam K. Preferential recognition of advanced glycation end products by serum antibodies and low-grade systemic inflammation in diabetes mellitus and its complications. Int J Biol Macromol. 2018; 118(Pt B):1884-91. doi.org/10.1016/j.ijbiomac.2018.07.033
- Qiao YC, Shen J, Hong XZ, Liang L, Bo CS, Sui Y, et al. Changes of regulatory T cells, transforming growth factor-beta and interleukin-10 in patients with type 1 diabetes mellitus: A systematic review and meta-analysis. Clin Immunol. 2016; 170:61-9. doi.org/10.1016/j.clim.2016.08.004
- Peeters SA, Engelen L, Buijs J, Jorsal A, Parving HH, Tarnow L, et al. Plasma matrix metalloproteinases are associated with incident cardiovascular disease and all-cause mortality in patients with type 1 diabetes: a 12-year follow-up study. Cardiovasc Diabetol. 2017; 16(1):55. doi.org/10.1186/s12933-017-0539-1
- White PC, Adhikari S, Grishman EK, Sumpter KM. A phase I study of anti-inflammatory therapy with rilonacept in adolescents and adults with type 1 diabetes mellitus. Pediatr Diabetes. 2018; 19(4):788-93. doi.org/10.1111/pedi.12634
- Al-Azzawi HH, Wade TE, Swartz-Basile DA, Wang S, Pitt HA, Zyromski NJ. Acute pancreatitis in obesity: adipokines and dietary fish oil. Dig Dis Sci. 2011; 56(8):2318-25. doi.org/10.1007/s10620-011-1626-x
- Miller EG, Sethi P, Nowson CA, Dunstan DW, Daly RM. Effects of progressive resistance training and weight loss versus weight loss alone on inflammatory and endothelial biomarkers in older adults with type 2 diabetes. Eur J Appl Physiol. 2017; 117(8):1669-78. doi.org/10.1007/s00421-017-3657-2
- Sharif K, Watad A, Coplan L, Lichtbroun B, Krosser A, Lichtbroun M, et al.The role of stress in the mosaic of autoimmunity. An overlooked association. AUTOIMMUN. 2018; 17(10):967-83. doi.org/10.1016/j.autrev.2018.04.005
- Liang M, Liwen Z, Yun Z, Yanbo, D., Jianping, C. Serum levels of IL-33 and correlation with IL-4, IL-17A, and hypergammaglobulinemia in patients with autoimmune hepatitis. Mediators Inflamm. 2018; 7964654. doi.org/10.1155/2018/7964654
- Keegan AD, Zamorano J, Keselman A, Heller NM. IL-4 and IL-13 Receptor Signaling From 4PS to Insulin Receptor Substrate 2: There and Back Again, a Historical View. Front Immunol. 2018: 9:1037. doi.org/10.3389/fimmu.2018.01037