Hyporesponsiveness to the anti-inflammatory action of interleukin-10 in type 2 diabetes

Abstract

Chronic low-grade inflammation contributes to the pathology and complications of type 2 diabetes (T2D). Interleukin-10 (IL10), an anti-inflammatory cytokine, is suggested to play a protective role in T2D. However, the impact of T2D on IL10 function has not been previously assessed. We examined the ability of IL10 to inhibit inflammation in human T2D immune cells and explored underlying mechanisms using macrophage models. IL10 was less effective at inhibiting tumour necrosis factor (TNF)-α secretion in T2D whole blood cultures, which was not explained by altered IL10 receptor surface expression. These findings were observed in macrophages exposed to high glucose, which demonstrated similar IL10 resistance or hyporesponsiveness. These findings were also not explained by changes in IL10 receptor protein or other downstream signaling proteins. High glucose was also shown to impair the ability of IL10 to activate STAT3, a downstream signaling protein of IL10. Treatment with the SHIP1 agonist, AQX-MN100, reversed IL10 hyporesponsiveness in macrophages cultured in high glucose and showed equal effectiveness at different glucose conditions. This data supports the idea that IL10 hyporesponsiveness may contribute to chronic inflammation in T2D. These novel findings suggest that strategies aimed to overcome IL10 hyporesponsiveness may hold therapeutic potential for reducing inflammation in T2D.

Antihyperglycemic effect of Sesbania grandiflora seed decoction on streptozotocin-induced diabetic mice: Inflammatory status and the role of interleukin-10

“…The mode of action of IL-10 in preventing diabetes was mostly linked to its properties as an anti-inflammatory cytokine [14,15,16,23,24]. However, the decrease of blood glucose in this research was not likely related to antiinflammatory activity of IL-10, since no inflammation occurred in any of the experimental groups.…”

“…[23][24] In particular, Goudy et al 14 and Goudy et al 15 found that IL-10 could be used to prevent type 1 diabetes in mice. The role of IL-10 in protection from type 2 diabetes was reported by Bary et al 16 The data were analized by Analysis of Variance (ANOVA) followed by Duncan's Multiple Range Test (DMRT).…”

“…IL-10 has a protective effect in type 1 diabetes [14][15] and type 2 diabetes. 16 Therefore, searching for herbal remedies capable of accelerating IL-10 production could be a rational strategy in the immunomodulatory therapy of diabetes treatment.…”

Metformin associated inflammation levels regulation in type 2 diabetes mellitus-tuberculosis coinfection patients – A case report

“…IL-10 is produced by macrophages 27,28 . In this study, the increasing 150. of IL-10 may happen not only due to macrophage related Th-2 activation but also due 151. to insulin attenuated anti-inflammation regulatory [29][30][31][32] .…”

“…IL-10 a major anti-inflammatory cytokines plays important role in metabolic disorder 143. such diabetes due its affect to insulin sensitivity 29 . IL-10 is produced by macrophages 27,28 .…”