Proinflammatory Cytokines Elevated in Patients With Intercritical Gout, and Linked to MSU Deposition Size and CV Risk Factors

Macrophage releasing cytokines
Researchers studied subclinical inflammation in intercritical gout and its association with the size of monosodium urate crystal deposition and cardiovascular risk factors.

Proinflammatory cytokines and metabolic proteins are elevated in patients with gout, with levels of cytokines linked to the estimated size of monosodium urate (MSU) crystal deposition as well as the number of cardiovascular risk factors, according to study results published in Rheumatology (Oxford).  

To analyze subclinical inflammation in intercritical gout, cytokine and adipokine plasma levels (interleukin [IL]-1β, IL-18, IL-6, sIL-6R, tumor necrosis factor [TNF] α, CXCL5, RANTES, leptin, resistin, and adiponectin) were quantified via secretome analysis. An indirect clinical classification was used to estimate size of the MSU crystal deposition, and cytokine levels were compared between patients with different crystal deposition size and healthy control participants. Associations between cytokine levels and the number of cardiovascular risk factors were also explored.

A total of 90 patients with gout with included in the current analysis. Higher levels of IL-18, sIL-6R, RANTES, leptin, and adiponectin were found in patients with gout compared with healthy control participants. Among patients with gout, with an increase in estimated crystal deposition size, there was an increase in IL-18, sIL-6R, and RANTES levels.

Patients were categorized into groups based on the presence of hypertension, hyperlipidemia, body mass index (BMI) greater than 30, or diabetes mellitus. In patients with hypertension, hyperlipidemia, or BMI greater than 30, leptin levels were higher. In patients with gout, hypertension was also associated with higher levels of IL-18, sIL-6R, resistin, and adiponectin; however, there were no associations observed with diabetes mellitus.

Comparisons between the number of cardiovascular risk factor and cytokine levels revealed a progressive increase in IL-18 and leptin levels related to the number of risk factors. Higher RANTES, sIL-6R, resistin, and adiponectin levels were also found in patients with risk factors. Researchers noted that patients with gout without cardiovascular risk factors had higher levels of IL-18, sIL-6R, RANTES, and leptin compared with healthy control participants without risk factors, which suggests that MSU crystal deposition may be involved in the increase in levels of these molecules.

Study limitations included the lack of direct crystal deposit measurement techniques and the fact that patient data were not analyzed based on flares.

Researchers concluded, “…cytokine changes, and the proinflammatory status they represent, may help to explain the increase in [cardiovascular] events in patients with [gout].” They added, “[These] data can help to better understand crystal MSU deposition consequences beyond acute flares” and “having a clinical classification of MSU crystal deposition can help to decide when [urate-lowering therapy] should begin.”

Disclosure: This study was supported by Grünental. Please see the original reference for a full list of authors’ disclosures.


Diaz-Torne C, Ortiz MA, Garcia-Guillen A, et al. The inflammatory role of silent urate crystal deposition in intercritical gout. Rheumatology (Oxford). Published online April 11, 2021. doi:10.1093/rheumatology/keab335