Reduced concentrations of the B cell cytokine interleukin 38 are associated with cardiovascular disease risk in overweight subjects

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.

Recent Updates on the Involvement of PI3K/AKT/mTOR Molecular Cascade in the Pathogenesis of Hyperproliferative Skin Disorders

“…Psoriasis is a chronic inflammatory skin disorder, in which skin-infiltrating T-helper (Th1, Th17, and Th22) lymphocytes promote keratinocyte hyperproliferation and terminal differentiation by releasing the pro-inflammatory cytokines IL-17A, IL-22, TNF-α, and IFN-γ (12)(13)(14)(15). IL-36 cytokines released by keratinocytes themselves also determine impaired keratinocyte maturation and cornification in psoriasis (16)(17)(18)(19). In addition, these cytokines upregulate PI3K/AKT/mTOR pathway, which in turn controls secretion of pro-inflammatory mediators by keratinocytes (20), enhances proliferation and impairs keratinocyte differentiation in skin affected by psoriasis (21).…”

The Pathological Mechanism and Potential Application of IL-38 in Autoimmune Diseases

“…MS, a chronic autoimmune inflammatory illness, can affect the CNS and result in severe disability (Gul et al, 2020). The typical clinical symptoms of MS are characterized by weakness, sensory loss, diplopia, decreased vision, etc (Cunniffe and Coles, 2021). Moreover, inflammation with demyelination and astrocyte proliferation and neurodegeneration are two pathological features of multiple sclerosis MS (Hauser and Cree, 2020).…”

“…Broadly speaking, IL-38 is secreted by various immune cells, for instance, B cells ( Xie et al, 2019 ). Notably, as a B cell product, the relative deficiency of IL-38 is related to increased systemic inflammation in metabolic diseases, cardiovascular, and aging ( de Graaf et al, 2021 ). Generally, IL-38 is expressed in human heart, thymus etc.…”

“…IL-38 plays a role in immune cells, for instance, B cells and T cells, while autoimmune diseases are related to immune cells ( Singh et al, 2012 ; van de Veerdonk et al, 2012 ; Romo-Tena et al, 2013 ; de Graaf et al, 2021 ). And IL-38 might impact the process of autoimmune diseases mediated via immune cells ( Garraud et al, 2018 ).…”

Interleukin-22: a potential therapeutic target in atherosclerosis

“…IL-38 is known as an anti-inflammatory factor that suppresses pro-inflammatory cytokine production by its receptors and protects against cardiovascular disease (Graaf et al 2021 ; Esmaeilzadeh et al 2019 ). Recently, IL-38 overexpression was found to inhibit hyperlipidemia and atherosclerosis in apoE −/− by alleviating inflammation (Yang et al 2018 ).…”