Serum uric acid increases in patients with systemic autoimmune rheumatic diseases after 3 months of treatment with TNF inhibitors
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In patients with gout, the serum uric acid (SUA) is usually lower during acute gouty attacks than during intercritical periods. It has been suggested that systemic inflammatory response can cause this phenomenon. The objective is to determine whether therapy with TNF inhibitors (TNFis) affects SUA levels in patients with systemic autoimmune rheumatic diseases (SARDs) and whether SUA changes correlate with pro-inflammatory cytokines or with the oxidative stress marker allantoin. In this study, SUA, CRP, creatinine, MCP-1, IFN-α2, IFN-γ, Il-1β, IL-6, IL-8, IL-10, IL-12, IL-17a, IL-18, IL-23, IL-33, TNF-α, and allantoin levels were measured prior to and after 3 months of TNFis treatment in patients with SARDs. The values obtained in the biochemical assays were then tested for associations with the patients’ demographic and disease-related data. A total of 128 patients (rheumatoid arthritis, n = 44; ankylosing spondylitis, n = 45; psoriatic arthritis, n = 23; and adults with juvenile idiopathic arthritis, n = 16) participated in this study. Among the entire patient population, SUA levels significantly increased 3 months after starting treatment with TNFis (279.5 [84.0] vs. 299.0 [102.0] μmol/l, p < 0.0001), while the levels of CRP, IL-6, IL-8, and MCP-1 significantly decreased. Male sex was the most powerful baseline predictor of ΔSUA in univariate and multivariate models. None of the measured laboratory-based parameters had statistically significant effects on the magnitude of ΔSUA. 3 months of anti-TNF therapy increased the levels of SUA in patients with SARDs, but neither the measured pro-inflammatory cytokines nor the oxidation to allantoin appeared responsible for this effect.
KeywordsUric acid Inflammation Rheumatic diseases Cytokines Oxidative stress
We would like to thank Dr. Laszlo Wenchich and the members of the Department of Clinical Biochemistry and Hematology (Institute of Rheumatology) for their kind assistance with the biochemical measurements.
All authors were involved in drafting the manuscript or revising it critically for content. LH planned and performed most of the measurements, conducted data analysis, and wrote the manuscript. MP conducted statistical data analysis and prepared the figures. HH and AM helped with measurements of cytokines and with analyzing data. PK and KK carried out mass spectrometric measurements. MH and BS provided scientific input and interpretation of data. JZ designed the project, supervised its conduct, and helped to write the manuscript. The final manuscript has been seen and approved by all authors.
This work was supported by the Charles University Research Grant GA UK no. 940517, the Ministry of Health of the Czech Republic (Institute of Rheumatology—Conceptual Development of Research Organization, 00023728), and the Czech Science Foundation, Grant no. 19-18005Y. LH was a recipient of the ARTICULUM Fellowship.
Compliance with ethical standards
Conflict of interest
All authors declare that there is no conflict of interest regarding the publication of this article.
All procedures in this study were in accordance with the ethical standards of the institutional and national research committee (Czech Multicentre Research Ethics Committee, no. 201611 S300 and Institutional Ethics Committee of Institute of Rheumatology, Prague, Czech Republic, no. 10113/2016) and with the 1964 Helsinki declaration and its later amendments.
- 4.Waldron JL, Ashby HL, Razavi C, Thomas OL, Chugh S, Deshpande S, Ford C, Gama R (2013) The effect of the systemic inflammatory response, as provoked by elective orthopaedic surgery, on serum uric acid in patients without gout: a prospective study. Rheumatology (Oxford, England) 52(4):676–678. https://doi.org/10.1093/rheumatology/kes327 CrossRefGoogle Scholar
- 5.Tsutani H, Yoshio N, Ueda T (2000) Interleukin 6 reduces serum urate concentrations. J Rheumatol 27(2):554Google Scholar
- 6.Urano W, Yamanaka H, Tsutani H, Nakajima H, Matsuda Y, Taniguchi A, Hara M, Kamatani N (2002) The inflammatory process in the mechanism of decreased serum uric acid concentrations during acute gouty arthritis. J Rheumatol 29(9):1950–1953Google Scholar
- 10.Kellogg EW 3rd, Fridovich I (1977) Liposome oxidation and erythrocyte lysis by enzymically generated superoxide and hydrogen peroxide. J Biol Chem 252(19):6721–6728Google Scholar
- 18.Lyngdoh T, Marques-Vidal P, Paccaud F, Preisig M, Waeber G, Bochud M, Vollenweider P (2011) Elevated serum uric acid is associated with high circulating inflammatory cytokines in the population-based Colaus study. PLoS One 6(5):e19901. https://doi.org/10.1371/journal.pone.0019901 CrossRefGoogle Scholar
- 23.Torres R, Macdonald L, Croll SD, Reinhardt J, Dore A, Stevens S, Hylton DM, Rudge JS, Liu-Bryan R, Terkeltaub RA, Yancopoulos GD, Murphy AJ (2009) Hyperalgesia, synovitis and multiple biomarkers of inflammation are suppressed by interleukin 1 inhibition in a novel animal model of gouty arthritis. Ann Rheum Dis 68(10):1602–1608. https://doi.org/10.1136/ard.2009.109355 CrossRefGoogle Scholar
- 24.Lopera-Mesa TM, Mita-Mendoza NK, van de Hoef DL, Doumbia S, Konate D, Doumbouya M, Gu W, Traore K, Diakite SA, Remaley AT, Anderson JM, Rodriguez A, Fay MP, Long CA, Diakite M, Fairhurst RM (2012) Plasma uric acid levels correlate with inflammation and disease severity in Malian children with Plasmodium falciparum malaria. PLoS One 7(10):e46424. https://doi.org/10.1371/journal.pone.0046424 CrossRefGoogle Scholar
- 26.Panoulas VF, Douglas KMJ, Milionis HJ, Nightingale P, Kita MD, Klocke R, Metsios GS, Stavropoulos-Kalinoglou A, Elisaf MS, Kitas GD (2007) Serum uric acid is independently associated with hypertension in patients with rheumatoid arthritis. J Hum Hypertens 22:177. https://doi.org/10.1038/sj.jhh.1002298 CrossRefGoogle Scholar
- 29.Walters HM, Pan N, Lehman TJ, Adams A, Kalliolias GD, Zhu YS, Santiago F, Nguyen J, Sitaras L, Cunningham-Rundles S, Walsh TJ, Toussi SS (2016) The impact of disease activity and tumour necrosis factor-α inhibitor therapy on cytokine levels in juvenile idiopathic arthritis. Clin Exp Immunol 184(3):308–317. https://doi.org/10.1111/cei.12782 CrossRefGoogle Scholar
- 32.Ware CF (2005) Network communications: lymphotoxins, LIGHT, and TNF. Annu Rev Immunol 23:787–819. https://doi.org/10.1146/annurev.immunol.23.021704.115719 CrossRefGoogle Scholar