ORIGINAL PAPER
Obesity and IL-21, IL-22, and IL-23 in low-grade inflammation: associations with nutrition and stimulant use
More details
Hide details
1
College of Medical Sciences, University of Rzeszów, Rzeszow, Poland
2
Department of Human Immunology, Faculty of Medicine, Collegium Medicum, University of Rzeszow, Rzeszow, Poland
These authors had equal contribution to this work
Submission date: 2025-05-23
Final revision date: 2026-03-11
Acceptance date: 2026-03-12
Online publication date: 2026-07-20
Corresponding author
Jacek Tabarkiewicz
Department of Human Immunology, Faculty of Medicine, Collegium Medicum, University of Rzeszow, Rzeszow, Poland
KEYWORDS
ABSTRACT
Introduction:
Interleukin (IL)-21, IL-22, and IL-23 have been most frequently evaluated in patients with autoimmune or inflammatory diseases. In contrast, data on these cytokines in obesity and obesity-related low-grade inflammation remain limited.
Material and Methods:
Serum concentrations of IL-21, IL-22, and IL-23 were analyzed in 84 obese individuals. Dietary intake was assessed using a nutrition questionnaire and a 3-day food diary. Body composition was evaluated using bioelectrical impedance analysis.
Results:
Within the obese cohort, IL-23 levels were negatively associated with body mass index (BMI). Alcohol consumption was associated with lower circulating IL-21 levels, while self-reported physical activity was associated with higher IL-23 concentrations. Dietary factors, including the amount and type of carbohydrates, dietary glycemic index, and the frequency of consumption of selected food groups (wholemeal pasta, fast food, cottage cheese, eggs, and fish), showed associations with circulating IL-21, IL-22, and IL-23 levels. In addition, dietary intake of retinol, niacin, riboflavin, omega-3 fatty acids, and -carotene was associated with variability in the concentrations of the studied cytokines.
Conclusions:
In obese individuals without autoimmune diseases, circulating IL-23 levels showed a negative association with BMI. Circulating levels of IL-21, IL-22, and IL-23 were associated with selected lifestyle and dietary factors, including alcohol consumption, physical activity, dietary patterns, and nutrient intake. These findings should be interpreted as exploratory and hypothesis-generating.
REFERENCES (52)
1.
Shoda H, Nagafuchi Y, Tsuchida Y, et al. (2017): Increased serum concentrations of IL-1 beta, IL-21 and Th17 cells in overweight patients with rheumatoid arthritis. Arthritis Res Ther 19: 111.
2.
Qu N, Xu M, Mizoguchi I, et al. (2013): Pivotal roles of T-helper 17-related cytokines, IL-17, IL-22, and IL-23, in inflammatory diseases. Clin Dev Immunol 2013: 968549.
3.
Halwani R, Sultana A, Vazquez-Tello A, et al. (2017): Th-17 regulatory cytokines IL-21, IL-23, and IL-6 enhance neutrophil production of IL-17 cytokines during asthma. J Asthma 9: 893-904.
4.
Bakhshimoghaddam F, Chaharlang R, Mansoori A, Dehghanseresht N (2024): Dietary inflammatory index and its association with risk of metabolic syndrome and its components: a systematic review and meta-analysis of observational studies. J Health Popul Nutr 43: 87.
5.
Battineni G, Sagaro GG, Chintalapudi N, et al. (2021): Impact of obesity-induced inflammation on cardiovascular diseases (CVD). Int J Mol Sci 22: 4798.
6.
Granata M, Skarmoutsou E, Trovato C, et al. (2017): Obesity, type 1 diabetes, and psoriasis: an autoimmune triple flip. Pathobiology 84: 71-79.
7.
Sglunda O, Mann HF, Hulejova H, et al. (2014). Decrease in serum interleukin-21 levels is associated with disease activity improvement in patients with recent-onset rheumatoid arthritis. Physiol Res 4: 475-481.
8.
Spolski R, Leonard WJ (2014): Interleukin-21: a double-edged sword with therapeutic potential. Nat Rev Drug Discov 5: 379-395.
9.
Fabrizi M, Marchetti V, Mavilio M, et al. (2014): IL-21 is a major negative regulator of IRF4-dependent lipolysis affecting Tregs in adipose tissue and systemic insulin sensitivity. Diabetes 63: 2086-2096.
10.
Woś I, Tabarkiewicz J (2021): Effect of interleukin-6, -17, -21, -22, and -23 and STAT3 on signal transduction pathways and their inhibition in autoimmune arthritis. Immunol Res 1: 26-42.
11.
Perusina Lanfranca M, Lin Y, Fang J, et al. (2016): Biological and pathological activities of interleukin-22. J Mol Med 5: 523-534.
12.
Paget C, Ivanov S, Fontaine J, et al. (2012): Interleukin-22 is produced by invariant natural killer T lymphocytes during influenza A virus infection: potential role in protection against lung epithelial damages. J Biol Chem 12: 8816-8829.
13.
Wang K, Zhou M, Si H, Ma J (2023): Gut microbiota-mediated IL-22 alleviates metabolic inflammation. Life Sci 334: 122229.
14.
Kochumon S, Hasan A, Al-Rashed F, et al. (2022): Increased adipose tissue expression of IL-23 associates with inflammatory markers in people with high LDL cholesterol. Cells 19: 3072.
15.
Wadolowska L (2005): Validation of food frequency questionnaire-FFQ Reproducibility assessment. Bromat Chem Toksykol 38: 27-33.
16.
Juncal-Ruiz M, Riesco-Dávila L, de la Foz VO, et al. (2018): The effect of excess weight on circulating inflammatory cytokines in drug-naïve first-episode psychosis individuals. J Neuroinflammation 15: 63.
17.
Landgren AJ, Jonsson CA, Bilberg A, et al. (2023): Serum IL-23 significantly decreased in obese patients with psoriatic arthritis six months after a structured weight loss intervention. Arthritis Res Ther 25: 131.
18.
Sumarac-Dumanovic M, Stevanovic D, Ljubic A, et al. (2009): Increased activity of interleukin-23/interleukin-17 proinflammatory axis in obese women. Int J Obes (Lond) 33: 151-156.
19.
Krueger JG, Eyerich K, Kuchroo VK, et al. (2024): IL-23 past, present, and future: a roadmap to advancing IL-23 science and therapy. Front Immunol 15: 1331217.
20.
Kochumon S, Bahman F, Albeloushi S, et al. (2025): Adipose tissue IL-23 is associated with fasting blood glucose and HbA1c in overweight/obese individuals. Front Endocrinol (Lausanne) 16: 1608846.
21.
Nogues EB, Auger S, Agus A, et al. (2025): REG3A and IL22 have opposite effects on fat accumulation in the liver in a high-fat diet. Sci Rep 15: 33733.
22.
Park O, Ki SH, Xu M, et al. (2015): Biologically active, high levels of interleukin-22 inhibit hepatic gluconeogenesis but do not affect obesity and its metabolic consequences. Cell Biosci 5: 25.
23.
Seyfried F, Springer R, Hoffmann A, et al. (2022): Gastric bypass surgery weight loss-independently induces gut IL-22 release in association with improved glycemic control in obese Zucker fatty rats. Metabol Open 17: 100212.
24.
Brito-Luna MJ, Villanueva-Quintero DG, Sandoval-Talamantes AK, et al. (2016): Correlation of IL-12, IL-22, and IL-23 in patients with psoriasis and metabolic syndrome. Preliminary report. Cytokine 85: 130-136.
25.
Kochumon S, Hasan A, Al-Rashed F, et al. (2022): Increased adipose tissue expression of IL-23 associates with inflammatory markers in people with high LDL cholesterol. Cells 11: 3072.
26.
Zou J, Chassaing B, Singh V, et al. (2018): Fiber-mediated nourishment of gut microbiota protects against diet-induced obesity by restoring IL-22-mediated colonic health. Cell Host Microbe 1: 41-45.
27.
Shih VF, Cox J, Kljavin NM, et al. (2014): Homeostatic IL-23 receptor signaling limits Th17 response through IL-22-mediated containment of commensal microbiota. Proc Natl Acad Sci U S A 38: 13942-13947.
28.
Chen HZ, Zeng YY, Cai GX, et al. (2024): Differential analysis of serum immunology and gut microbiota in patients with gastrointestinal diseases. Front Microbiol 15: 1323842.
29.
Torquati L, Coombes JS, Murray L, et al. (2019): Fibre intake is independently associated with increased circulating interleukin-22 in individuals with metabolic syndrome. Nutrients 11: 8.
30.
Zou J, Reddivari L, Shi Z, et al. (2021): Inulin fermentable fiber ameliorates type I diabetes via IL-22 and short-chain fatty acids in experimental models. Cell Mol Gastroenterol Hepatol 12: 983-1000.
31.
Lo Conte M, Antonini Cencicchio M, Ulaszewska M, et al. (2023): A diet enriched in omega-3 PUFA and inulin prevents type 1 diabetes by restoring gut barrier integrity and immune homeostasis in NOD mice. Front Immunol 13: 1089987.
32.
Shi Z, Wu X, Santos Rocha C, et al. (2021): Short-term western diet intake promotes IL-23-mediated skin and joint inflammation accompanied by changes to the gut microbiota in mice. J Invest Dermatol 141: 1780-1791.
33.
Barros KV, Flor Silveira VL, Laranjeira MS, et al. (2017): Evidence for involvement of IL-9 and IL-22 in cows’ milk allergy in infants. Nutrients 10: 1048.
34.
Souwer Y, Szegedi K, Kapsenberg ML, de Jong EC (2010): IL-17 and IL-22 in atopic allergic disease. Curr Opin Immunol 6: 821-826.
35.
Kumazawa T, Kotake K, Nishimura A, et al. (2020): Isolation of food-derived bacteria inducing interleukin-22 in B cells. Biosci Microbiota Food Health 39: 1-9.
36.
Mora JR, Iwata M, von Andrian UH (2008): Vitamin effects on the immune system: vitamins A and D take centre stage. Nat Rev Immunol 9: 685-698.
37.
Miller JK, Harrison MT, D’Andrea A, et al. (2013): -carotene biosynthesis in probiotic bacteria. Probiotics Antimicrob Proteins 5: 69-80.
38.
Jie Z, Liang Y, Yi P, et al. (2017): Retinoic acid regulates immune responses by promoting IL-22 and modulating S100 proteins in viral hepatitis. J Immunol 9: 3448-3460.
39.
Mielke LA, Jones SA, Raverdeau M, et al. (2013): Retinoic acid expression associates with enhanced IL-22 production by T cells and innate lymphoid cells. J Exp Med 210: 1117-1124.
40.
Korkmaz K, Düzova H, Çetin Taşlidere A, et al. (2023): Effect of high-intensity exercise on endoplasmic reticulum stress and proinflammatory cytokine levels. Sci Sports 38: 428.e1-428.e10.
41.
Polak-Szczybyło E, Tabarkiewicz J (2024): Influence of dietary and lifestyle factors on levels of inflammatory markers (IL-6, IFN- and TNF-) in obese subjects. Cent Eur J Immunol 49: 19-25.
42.
Beech RD, Qu J, Leffert JJ, et al. (2012): Altered expression of cytokine signaling pathway genes in peripheral blood cells of alcohol dependent subjects: preliminary finding. Alcohol Clin Exp Res 36: 1487-1496.
43.
Mootha A, Malaiappan S, Milstein DMJ, et al. (2021): Comparison of interleukin-21 levels and its correlation with clinical parameters among healthy individuals, chronic periodontitis, and aggressive periodontitis. J Clin Transl Res 7: 84-92.
44.
Komiyama M, Wada H, Yamakage H, Satoh-Asahara N, Sunagawa Y, Morimoto T, Ozaki Y, Shimatsu A, Takahashi Y, Hasegawa K (2018): Analysis of changes on adiponectin levels and abdominal obesity after smoking cessation. PLoS One 8: e0201244.
45.
Janiszewska J, Ostrowska J, Szostak-Węgierek D (2021): The influence of nutrition on adiponectin – A narrative review. Nutrients 13(5): 1394.
46.
Sonnenberg GF, Monticelli LA, Elloso MM, et al. (2011): CD4(+) lymphoid tissue-inducer cells promote innate immunity in the gut. Immunity 34: 122-134.
47.
Murphy CA, Langrish CL, Chen Y, et al. (2004): Divergent pro- and anti-inflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J Exp Med 12: 1951-1957.
48.
Zhang GX, Gran B, Yu S, et al. (2003): Induction of experimental autoimmune encephalomyelitis in IL-12 receptor-beta2-deficient mice: IL-12 responsiveness is not required in the pathogenesis of inflammatory demyelination in the central nervous system. J Immunol 170: 2153-2160.
49.
Taleb S, Tedgui A, Mallat Z (2010): Adaptive T cell immune responses and atherosclerosis. Curr Opin Pharmacol 10: 197-202.
50.
Liang SC, Tan XY, Luxenberg DP, et al. (2006): Interleukin-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med 10: 2271-2279.
51.
Kwiatek M, Kwaśniewski W, Gęca T, et al. (2025): Dysregulation of Treg/Th17 balance and intracellular expression of IL-21 and IL-22 in the pathogenesis of gestational hypertension. J Clin Med 2025; 14: 7288.
52.
García-Domínguez M (2025): The role of IL-23 in the development of inflammatory diseases. Biology 14: 347.