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- Title
Reduced concentrations of the B cell cytokine interleukin 38 are associated with cardiovascular disease risk in overweight subjects.
- Authors
Graaf, Dennis M.; Jaeger, Martin; Munckhof, Inge C. L.; Horst, Rob; Schraa, Kiki; Zwaag, Jelle; Kox, Matthijs; Fujita, Mayumi; Yamauchi, Takeshi; Mercurio, Laura; Madonna, Stefania; Rutten, Joost H.W.; Graaf, Jacqueline; Riksen, Niels P.; Veerdonk, Frank L.; Netea, Mihai G.; Joosten, Leo A.B.; Dinarello, Charles A.
- 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.
- Subjects
B cells; CYTOKINES; INTERLEUKIN-21; BODY mass index; OBESITY; C-reactive protein
- Publication
European Journal of Immunology, 2021, Vol 51, Issue 3, p662
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201948390