Serum concentrations of IL-1β and IL-18 in gout patients out of flare are not connected to cardiovascular alterations


Key words: gout patients out of flare; serum concentrations of IL-1β and IL-18; cardiovascular alterations

How to Cite

Gancheva, R., Velikova, T., Kundurzhiev, T., Kolarov, Z., & Koundurdjiev, A. (2019). Serum concentrations of IL-1β and IL-18 in gout patients out of flare are not connected to cardiovascular alterations. Rheumatology (Bulgaria), 27(4), 18-26.


Background: In the literature there are reports that the key interleukins, IL-1β and IL-18, for the initiation and maintenance of gouty inflammation are associated with renal and cardiovascular disorders. They have a major regulatory function in the innate immune response and in vascular pathology. Objective: We aimed to determine serum levels of IL-1β and IL-18 in controls with inactivated osteoarthritis, patients with asymptomatic hyperuricemia, gouty arthritis without tophi subjects and gouty tophi individuals out of flare, and to establish whether their serum concentrations are connected to ultrasound alterations of the kidneys and heart. Materials and methods: The study is cross-sectional in design. A total of 83 consecutive patients were included: 18 with inactivated osteoarthritis, 29 with asymptomatic hyperuricemia, 22 gouty arthritis without tophi and 18 gouty tophi individuals out of flare. Serum interleukin concentrations were determined by enzyme-linked immunosorbent assay (ELISA) with Human IL-1β and IL-18 ELISA kits (Platinum, eBioscience, Vienna, Austria). By applying ultrasound were measured: renal resistive index (RRI) with 3.5 MHz transducer working with pulse Doppler frequency of 2.5 MHz and left ventricular mass index (LVMi), determined with 2.5 MHz transducer Phased Array. Data were analyzed by One-Sample Kolmogorov-Smirnov, ANOVA, Tukey HSD, Kruskal Wallis, Mann-Whitney and Fisher’s exact test. Correlational analyzes were performed by using the Spearman correlation coefficient. Results: In gouty tophi subjects serum IL-1β level was undetectable compared to the other three groups, (p<0.001). The serum concentration of IL-18 was comparable across the groups, (p=0.154). Given that the level of IL-1β was undetectable in gouty tophi patients, a correlation analysis in this group with serum uric acid concentration, RRI and LVMi was not performed. In the remaining three groups, which had values of IL-1β above zero, we did not detect an association with the above mentioned parameters. No correlation was found between IL-18 concentration and serum uric acid, RRI and LVMi in the groups. Conclusion: We suggest that serum IL-1β and IL-18 levels do not reflect the severity of the disease and cardiovascular risk in the examined gout patients.


  1. Dinarello CA. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood, 2011, 117(14), 3720-3732.
  2. Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with Canakinumab for atherosclerotic disease. N Engl J Med, 2017, 377(12), 1119-1131.
  3. Mallat Z, Heymes C, Corbaz A, et al. Evidence for altered interleukin 18 (IL)-18 pathway in human heart failure. FASEB J, 2004, 18(14), 1752-1754.
  4. Woldback PR, Sande JB, Stromme TA, et al. Daily administration of interleukin-18 causes myocardial dysfunction in healthy mice. Am J Physiol Heart Circ Physiol, 2005, 289 (2), H708-14.
  5. Punzi L, Scanu A, Ramonda R, Olivera F. Gout as autoinflammatory disease: new mechanisms for more appropriated treatment targets. Autoimmunity Reviews, 2012, 12(1), 66-71.
  6. Lubas A, Kade G, Niemczyk S. Renal resistive index as a marker of vascular damage in cardiovascular diseases. Int Urol Nephrol, 2014, 46(2), 395-402. doi:10.1007/s11255-013-0528-6
  7. Laukkanen A, Khan H, Kurl S, et al. Left Ventricular Mass and the Risk of Sudden Cardiac Death: A Population-Based Study. J Am Heart Assoc, 2014, 3:e001285. doi: 10.1161/JAHA.114.001285
  8. Wallace SL, Robinson H, Masi AT, et al. Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum, 1977, 20(3), 895-900.
  9. National Kidney Foundation K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis, 2002, S1-S266.
  10. Heine GH, Gerhart MK, Ulrich C, et al. Renal Doppler resistance indices are associated with systemic atherosclerosis in kidney transplant recipients. Kidney Int, 2005, 68, 878-885.
  11. Lang RM, Beirig M, Devereux RB, et al. Chamber Quantification Writing Group; American Society of Echocardiography's Guidelines and Standards Committee; European Association of Echocardiography. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr, 2005, 18, 1440-1463.
  12. Nowak KL, Chonchol M, Ikizler TA, et al. IL-1 inhibition and vascular function in CKD. J Am Soc Nephrol, 2017, 28(3), 971-980.
  13. Cauwenberghs N, Kuznetsova T. Determinants and Prognostic Significance of the Renal Resistive Index. Pulse (Basel), 2016, 3(3-4), 172-178. doi:10.1159/000442445
  14. Ørn S, Ueland T, Manhenke C, Sandanger Ø, et al. Increased interleukin-1β levels are associated with left ventricular hypertrophy and remodelling following acute ST segment elevation myocardial infarction treated by primary percutaneous coronary intervention. J Intern Med, 2012, 272(3), 267-276.
  15. Rao GN, Corson MA, Berk BC. Uric acid stimulates vascular smooth muscle cell proliferation by increasing platelet derived growth factor A-chain expression. J Biol Chem, 1991, 266(13), 8604-8608.
  16. Galea J, Armstrong J, Gadsdon P, et al. Interleukin-1 beta in coronary arteries of patients with ischemic heart disease. Arterioscler Thromb Vasc Biol, 1996, 16(8), 1000-1006.
  17. Yano T, Nozaki Y, Kinoshita K, et al. The pathophysiological role of IL-18Rα in renal ischemia/reperfusion injury. Lab Invest, 2015, 95(1), 78-91.
  18. Parikh CR, Mishra J, Thiessen-Philbrook H, et al. Urinary IL-18 is an early predictive biomarker of acute kidney injury after cardiac surgery. Kidney Int, 2006, 70:199-203.
  19. ÖZzbïçer S, Uluçam ZM. Association Between Interleukin-18 Level and Left Ventricular Mass Index in Hypertensive Patients. Korean Circ J, 2017, 47(2), 238-244. doi:10.4070/kcj.2016.0351
  20. Blankenberg S, Tiret L, Bickel C, et al. IL-18 is a strong predictor of cardiovascular death in stable and unstable angina. Circulation, 2002, 106(1), 24-30.
Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.