Reduced concentrations of the B cell cytokine interleukin 38 are associated with cardiovascular disease risk in overweight subjects. Issue 3 (19th November 2020)

• Record Type: Journal Article
• Authors: de Graaf, Dennis M.; Jaeger, Martin; van den Munckhof, Inge C. L.; ter Horst, Rob; Schraa, Kiki; Zwaag, Jelle; Kox, Matthijs; Fujita, Mayumi; Yamauchi, Takeshi; Mercurio, Laura; Madonna, Stefania; Rutten, Joost H.W.; de Graaf, Jacqueline; Riksen, Niels P.; van de Veerdonk, Frank L.; Netea, Mihai G.; Joosten, Leo A.B.; Dinarello, Charles A.
• Is Part Of: European journal of immunology. Volume 51:Issue 3(2021)
• Page Start: 662
• Page End: 671
• Publication Date: 2020-11-19
• Subjects: IL‐38 -- Cardiovascular disease risk -- B cells -- Inflammation -- Obesity; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201948390
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract: The IL‐1 family member IL‐38 (IL1F10) suppresses inflammatory and autoimmune conditions. Here, we report that plasma concentrations of IL‐38 in 288 healthy Europeans correlate positively with circulating memory B cells and plasmablasts. IL‐38 correlated negatively with age ( p = 0.02) and was stable in 48 subjects for 1 year. In comparison with primary keratinocytes, IL1F10 expression in CD19 + B cells from PBMC was lower, whereas cell‐associated IL‐38 expression was comparable. In vitro, IL‐38 is released from CD19 + B cells after stimulation with rituximab. Intravenous LPS in humans failed to induce circulating IL‐38, compared to 100‐fold induction of IL‐6 and IL‐1 receptor antagonist. In a cohort of 296 subjects with body mass index > 27 at high risk for cardiovascular disease, IL‐38 plasma concentrations were significantly lower than in healthy subjects ( p < 0.0001), and lowest in those with metabolic syndrome ( p < 0.05). IL‐38 also correlated inversely with high sensitivity C‐reactive protein ( p < 0.01), IL‐6, IL‐1Ra, and leptin ( p < 0.05). We conclude that a relative deficiency of the B cell product IL‐38 is associated with increased systemic inflammation in aging, cardiovascular and metabolic disease, and is consistent with IL‐38 as an anti‐inflammatory cytokine. Abstract : We propose that circulating B cells are a major source of the anti‐inflammatory cytokine interleukin 38 (IL‐38). Circulating IL‐38 concentrations are reduced by old age, being overweight and having metabolic syndrome. In overweight subjects, a relative IL‐38 deficiency is associated with chronic inflammation and increased cardiovascular disease risk.