Abstract
Background
Cardiovascular diseases due to atherosclerosis represent the major cause of disability and mortality in old age subjects. The atherosclerotic process is linked to a low grade of systemic inflammation with the involvement of many cytokines and inflammatory proteins. Among them, evidence from animal studies suggests that IL-13 has a protective property. However, the role of IL-13 in the pathogenesis of atherosclerosis in humans is still unknown.
Aims
With this study, we aim to investigate a potential association between IL-13 and carotid intima-media thickness (IMT) in old age subjects.
Methods
This is a retrospective study conducted among 79 old age subjects (over 75 years old). All subjects underwent IMT assessment by high-resolution B-mode ultrasonography and IL-13 measurement in serum by ELISA.
Results
Subjects (41 M/38F) had a mean age of 81.0 ± 4.5 years and were mostly overweight. Stratifying the whole cohort by IMT thickness (IMT ≤ 0.9, n = 17; IMT ≥ 1 and ≤ 1.3, n = 50; IMT ≥ 1.4, n = 12) among the main variables explored, only BMI and triglycerides differed among groups, having subjects with higher IMT significantly higher BMI and lower triglycerides. Serum IL-13 levels significantly differed among groups having subjects with IMT ≥ 1.4 lower levels as compared to other groups (p < 0.0001). In all sample population, IMT values significantly correlate with IL-13 levels (r = − 0.454, p < 0.0001). Indeed, a linear regression analysis showed that independent of age, gender, body mass index, triglycerides, systolic blood pressure, statin use and smoking habit, lower IL-13 serum levels were associated with higher IMT values.
Conclusions
IL-13, an anti-inflammatory cytokine, may have a protective role in the human atherosclerotic process. It could be used as an effective and promising novel therapeutic target development.
Similar content being viewed by others
References
Yeates K, Lohfeld L, Sleeth J et al (2015) A global perspective on cardiovascular disease in vulnerable populations. Can J Cardiol 31:1081. https://doi.org/10.1016/J.CJCA.2015.06.035
Hansson GK (2005) Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352:1685–1695. https://doi.org/10.1056/NEJMra043430
Duncan BB, Schmidt MI, Pankow JS et al (2003) Low-grade systemic inflammation and the development of type 2 diabetes: the atherosclerosis risk in communities study. Diabetes 52:1799–1805
Frostegård J, Ulfgren A-K, Nyberg P et al (1999) Cytokine expression in advanced human atherosclerotic plaques: the dominance of pro-inflammatory (Th1) and macrophage-stimulating cytokines. Atherosclerosis 145:33–43. https://doi.org/10.1016/S0021-9150(99)00011-8
Cardilo-Reis L, Gruber S, Schreier SM et al (2012) Interleukin-13 protects from atherosclerosis and modulates plaque composition by skewing the macrophage phenotype. EMBO Mol Med 4:1072–1086. https://doi.org/10.1002/emmm.201201374
Minty A, Chalon P, Derocq J-M et al (1993) Interleukin-13 is a new human lymphokine regulating inflammatory and immune responses. Nature 362:248–250. https://doi.org/10.1038/362248a0
Darkhal P, Gao M, Ma Y et al (2015) Blocking high-fat-diet-induced obesity, insulin resistance and fatty liver by overexpression of Il-13 gene in mice. Int J Obes 39:1292–1299. https://doi.org/10.1038/ijo.2015.52
Nair SB, Malik R, Khattar RS (2012) Carotid intima-media thickness: ultrasound measurement, prognostic value and role in clinical practice. Postgrad Med J 88:694–699. https://doi.org/10.1136/postgradmedj-2011-130214
van den Oord SCH, Sijbrands EJG, ten Kate GL et al (2013) Carotid intima-media thickness for cardiovascular risk assessment: Systematic review and meta-analysis. Atherosclerosis 228:1–11. https://doi.org/10.1016/J.ATHEROSCLEROSIS.2013.01.025
Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”; a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198
Katz S, Ab Ford, Rw Moskowitz et al (1963) Studies of illness in the aged. The index of ADL: a standardized measure of biological and psychosocial function. JAMA 185:914–919
Graf C (2008) The lawton instrumental activities of daily living scale. AJN, Am J Nurs 108:52–62. https://doi.org/10.1097/01.NAJ.0000314810.46029.74
Ravani A, Werba JP, Frigerio B et al (2015) Assessment and relevance of carotid intima-media thickness (C-IMT) in primary and secondary cardiovascular prevention. Curr Pharm Des 21:1164–1171. https://doi.org/10.2174/1381612820666141013121545
Libby P (2012) Inflammation in atherosclerosis. Arterioscler Thromb Vasc Biol 32:2045–2051. https://doi.org/10.1161/ATVBAHA.108.179705
Libby P (2002) Inflammation in atherosclerosis. Nature 420:868–874. https://doi.org/10.1038/nature01323
Zhu J (2015) T helper 2 (Th2) cell differentiation, type 2 innate lymphoid cell (ILC2) development and regulation of interleukin-4 (IL-4) and IL-13 production. Cytokine 75:14–24. https://doi.org/10.1016/j.cyto.2015.05.010
Doran E, Cai F, Holweg CTJ et al (2017) Interleukin-13 in asthma and other eosinophilic disorders. Front Med 4:139. https://doi.org/10.3389/fmed.2017.00139
Martínez-Reyes CP, Gómez-Arauz AY, Torres-Castro I et al (2018) Serum levels of interleukin-13 increase in subjects with insulin resistance but do not correlate with markers of low-grade systemic inflammation. J Diabetes Res 2018:1–11. https://doi.org/10.1155/2018/7209872
Madhumitha H, Mohan V, Deepa M et al (2014) Increased Th1 and suppressed Th2 serum cytokine levels in subjects with diabetic coronary artery disease. Cardiovasc Diabetol 13:1. https://doi.org/10.1186/1475-2840-13-1
Cardilo-Reis L, Gruber S, Schreier SM et al (2012) Interleukin-13 protects from atherosclerosis and modulates plaque composition by skewing the macrophage phenotype. EMBO Mol Med 4:1072. https://doi.org/10.1002/EMMM.201201374
Bäck M, Hansson GK (2015) Anti-inflammatory therapies for atherosclerosis. Nat Rev Cardiol 12:199–211. https://doi.org/10.1038/nrcardio.2015.5
Everett BM, Pradhan AD, Solomon DH et al (2013) Rationale and design of the cardiovascular inflammation reduction trial: a test of the inflammatory hypothesis of atherothrombosis. Am Heart J 166:199–207. https://doi.org/10.1016/j.ahj.2013.03.018
Ridker PM, Thuren T, Zalewski A et al (2011) Interleukin-1β inhibition and the prevention of recurrent cardiovascular events: rationale and design of the canakinumab anti-inflammatory thrombosis outcomes study (CANTOS). Am Heart J 162:597–605. https://doi.org/10.1016/j.ahj.2011.06.012
Ridker PM, Everett BM, Thuren T et al (2017) Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 377:1119–1131. https://doi.org/10.1056/NEJMoa1707914
Funding
This project was supported by Fondazione Cassa di Risparmio di Perugia (cod: 2017.0278.021).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no competing interests.
Statement of human and animal rights
The study is carried in accordance with the 1964 Helsinki Declaration and its later amendments and with the ethical standards of the institutional ethics committee, and was approved by the ethics committee of the University of Perugia, Perugia, Italy (INFStudy, Registry CEAS N: 3097/17).
Informed consent
All subjects provided written informed consent to participate in the study.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Boccardi, V., Paolacci, L., Croce, M.F. et al. Lower serum levels of IL-13 is associated with increased carotid intima-media thickness in old age subjects. Aging Clin Exp Res 32, 1289–1294 (2020). https://doi.org/10.1007/s40520-019-01313-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40520-019-01313-4