Level of IL-6, TNF, and IL-1β and Age-related Diseases: a Systematic Review and Meta-analysis

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2024 Mar 18

PMID 38495887

Authors

Anna Tylutka

Lukasz Walas

Agnieszka Zembron-Lacny

Affiliations

Soon will be listed here.

Abstract

Introduction: Chronic low-grade inflammation is an important aspect of morbidity and mortality in older adults. The level of circulating pro-inflammatory cytokines (interleukin (IL)-6, tumor necrosis factor (TNF) or IL-1β) is a risk factor in cardiovascular and neurodegenerative diseases and is also associated with sarcopenia and frailties. The objective of this study was to assess each cytokine: IL-6, TNF, and IL-1β separately in the elderly with comorbidities against controls without diseases according to the data published in the available literature.

Methods: The electronic bibliographic PubMed database was systematically searched to select all the relevant studies published up to July 2023. The total number of the subjects involved in the meta-analysis included patients with diseases (=8154) and controls (=33967).

Results: The overall concentration of IL-6 was found to be higher in patients with diseases compared to controls and the difference was statistically significant, with a -value of <0.001 (SMD, 0.16; 95% CI, 0.12-0.19). The heterogeneity was considerable with Q = 109.97 (P <0.0001) and I = 79.2%. The potential diagnostic usefulness of IL-6 was confirmed by odds ratio (OR) analysis (OR: 1.03, 95% CI (1.01; 1.05), =0.0029). The concentration of both TNF and IL-1β was elevated in the control group compared to patients and amounted to SMD -0.03; 95% CI, -0.09-0.02, -value 0.533 and SMD-0.29; 95% CI, -0.47- -0.12; = 0.001, respectively. For TNF, however, the difference was statistically insignificant.

Discussion: IL-6, unlike TNF and IL-1β, could be a useful and convenient marker of peripheral inflammation in older adults with various comorbidities.

Citing Articles

Changes in Concentration of Selected Biomarkers of Exposure in Users of Classic Cigarettes, E-Cigarettes, and Heated Tobacco Products-A Narrative Review.

Sniadach J, Kicman A, Michalska-Falkowska A, Jonczyk K, Waszkiewicz N Int J Mol Sci. 2025; 26(5).

PMID: 40076424 PMC: 11898610. DOI: 10.3390/ijms26051796.

Cytokine Signature Unveils Subgroups of Patients With Immune-Mediated Sensory Neuronopathies.

Moritz C, Tholance Y, Borowczyk C, Jospin F, Paul S, Antoine J J Peripher Nerv Syst. 2025; 30(1):e70008.

PMID: 40037793 PMC: 11879705. DOI: 10.1111/jns.70008.

A Panel of Diverse Inflammatory Biomarkers Is Not Associated with BMI-Calibrated Obesity nor with Dyslipidemia or Dysglycemia in Clinically Healthy Adults Aged 20 to 40 Years.

Sater M, Malalla Z, Ali M, Giha H Int J Environ Res Public Health. 2025; 22(2).

PMID: 40003433 PMC: 11855404. DOI: 10.3390/ijerph22020207.

Beyond Amyloid and Tau: The Critical Role of Microglia in Alzheimer's Disease Therapeutics.

Dias D, Socodato R Biomedicines. 2025; 13(2).

PMID: 40002692 PMC: 11852436. DOI: 10.3390/biomedicines13020279.

From Bench to Bedside: Translating Cellular Rejuvenation Therapies into Clinical Applications.

Saliev T, Singh P Cells. 2025; 13(24.

PMID: 39768144 PMC: 11674796. DOI: 10.3390/cells13242052.

References

Wan X, Wang W, Liu J, Tong T . Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014; 14:135. PMC: 4383202. DOI: 10.1186/1471-2288-14-135. View

Liberale L, Badimon L, Montecucco F, Luscher T, Libby P, Camici G . Inflammation, Aging, and Cardiovascular Disease: JACC Review Topic of the Week. J Am Coll Cardiol. 2022; 79(8):837-847. PMC: 8881676. DOI: 10.1016/j.jacc.2021.12.017. View

Furman D, Campisi J, Verdin E, Carrera-Bastos P, Targ S, Franceschi C . Chronic inflammation in the etiology of disease across the life span. Nat Med. 2019; 25(12):1822-1832. PMC: 7147972. DOI: 10.1038/s41591-019-0675-0. View

Mehta M, Louissaint J, Parikh N, Long M, Tapper E . Cognitive Function, Sarcopenia, and Inflammation Are Strongly Associated with Frailty: A Framingham Cohort Study. Am J Med. 2021; 134(12):1530-1538. PMC: 9004665. DOI: 10.1016/j.amjmed.2021.07.012. View

Sanchez-Castellano C, Martin-Aragon S, Bermejo-Bescos P, Vaquero-Pinto N, Miret-Corchado C, Merello de Miguel A . Biomarkers of sarcopenia in very old patients with hip fracture. J Cachexia Sarcopenia Muscle. 2020; 11(2):478-486. PMC: 7113494. DOI: 10.1002/jcsm.12508. View

Kaneko N, Kurata M, Yamamoto T, Morikawa S, Masumoto J . The role of interleukin-1 in general pathology. Inflamm Regen. 2019; 39:12. PMC: 6551897. DOI: 10.1186/s41232-019-0101-5. View

De Martinis M, Franceschi C, Monti D, Ginaldi L . Inflamm-ageing and lifelong antigenic load as major determinants of ageing rate and longevity. FEBS Lett. 2005; 579(10):2035-9. DOI: 10.1016/j.febslet.2005.02.055. View

Varadhan R, Yao W, Matteini A, Beamer B, Xue Q, Yang H . Simple biologically informed inflammatory index of two serum cytokines predicts 10 year all-cause mortality in older adults. J Gerontol A Biol Sci Med Sci. 2013; 69(2):165-73. PMC: 4038244. DOI: 10.1093/gerona/glt023. View

Boraschi D . What Is IL-1 for? The Functions of Interleukin-1 Across Evolution. Front Immunol. 2022; 13:872155. PMC: 9020223. DOI: 10.3389/fimmu.2022.872155. View

10.

Maggio M, Guralnik J, Longo D, Ferrucci L . Interleukin-6 in aging and chronic disease: a magnificent pathway. J Gerontol A Biol Sci Med Sci. 2006; 61(6):575-84. PMC: 2645627. DOI: 10.1093/gerona/61.6.575. View

11.

Xing Z, Gauldie J, Cox G, Baumann H, Jordana M, Lei X . IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses. J Clin Invest. 1998; 101(2):311-20. PMC: 508569. DOI: 10.1172/JCI1368. View

12.

Ershler W, Keller E . Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty. Annu Rev Med. 2000; 51:245-70. DOI: 10.1146/annurev.med.51.1.245. View

13.

Chu W . Tumor necrosis factor. Cancer Lett. 2012; 328(2):222-5. PMC: 3732748. DOI: 10.1016/j.canlet.2012.10.014. View

14.

Tattersall M, Dasiewicz A, McClelland R, Jarjour N, Korcarz C, Mitchell C . Persistent Asthma Is Associated With Carotid Plaque in MESA. J Am Heart Assoc. 2022; 11(23):e026644. PMC: 9851438. DOI: 10.1161/JAHA.122.026644. View

15.

Garcia J, Splenser A, Kramer J, Alsarraj A, Fitzgerald S, Ramsey D . Circulating inflammatory cytokines and adipokines are associated with increased risk of Barrett's esophagus: a case-control study. Clin Gastroenterol Hepatol. 2013; 12(2):229-238.e3. PMC: 3899092. DOI: 10.1016/j.cgh.2013.07.038. View

16.

Bauer J, Bauer T, Kalb T, Taga T, Lengyel G, Hirano T . Regulation of interleukin 6 receptor expression in human monocytes and monocyte-derived macrophages. Comparison with the expression in human hepatocytes. J Exp Med. 1989; 170(5):1537-49. PMC: 2189492. DOI: 10.1084/jem.170.5.1537. View

17.

Ferentinos P, Maratou E, Antoniou A, Serretti A, Smyrnis N, Moutsatsou P . Interleukin-1 Beta in Peripheral Blood Mononuclear Cell Lysates as a Longitudinal Biomarker of Response to Antidepressants: A Pilot Study. Front Psychiatry. 2022; 12:801738. PMC: 8738167. DOI: 10.3389/fpsyt.2021.801738. View

18.

Wong C, Ho C, Ko F, Chan C, Ho A, Hui D . Proinflammatory cytokines (IL-17, IL-6, IL-18 and IL-12) and Th cytokines (IFN-gamma, IL-4, IL-10 and IL-13) in patients with allergic asthma. Clin Exp Immunol. 2001; 125(2):177-83. PMC: 1906135. DOI: 10.1046/j.1365-2249.2001.01602.x. View

19.

Hubbard R, OMahony M, Savva G, Calver B, Woodhouse K . Inflammation and frailty measures in older people. J Cell Mol Med. 2009; 13(9B):3103-9. PMC: 4516469. DOI: 10.1111/j.1582-4934.2009.00733.x. View

20.

Morawin B, Tylutka A, Bielewicz F, Zembron-Lacny A . Diagnostics of inflammaging in relation to sarcopenia. Front Public Health. 2023; 11:1162385. PMC: 10351926. DOI: 10.3389/fpubh.2023.1162385. View