Low Production Capacity of Interleukin-10 Associates With the Metabolic Syndrome and Type 2 Diabetes

Abstract

It has been suggested that the metabolic syndrome and type 2 diabetes are manifestations of the inflammatory host response. This host response is orchestrated by the production of pro-and anti-inflammatory cytokines that are under genetic control. We therefore hypothesized that a low production capacity of interleukin-10 (IL-10), a centrally operating cytokine with strong anti-inflammatory properties, associates with the metabolic syndrome and type 2 diabetes in old age. In the current study, 599 inhabitants of the city of Leiden, age 85 years, were visited at their place of residence. The production capacity of the anti-inflammatory cytokine IL-10 was assessed in a whole-blood assay in which lipopolysaccharide was used as a stimulus. Serum concentrations of lipids, lipoproteins, glucose, and HbA 1c were determined, and a history of type 2 diabetes was obtained. Serum concentrations of total cholesterol, LDL cholesterol, triglycerides, glucose, and HbA 1c gradually decreased over strata representing higher IL-10 production capacity, whereas the concentration of HDL cholesterol gradually increased (all P < 0.01). The odds ratio for type 2 diabetes was 2.7 (95% confidence interval 1.5-4.9) when subjects with the lowest IL-10 production capacity were compared with those with the highest IL-10 production capacity. These findings showed that low IL-10 production capacity (i.e., a proinflammatory response) is associated with the metabolic syndrome and type 2 diabetes.

Adeno-associated virus vector-mediated interleukin-10 gene transfer inhibits atherosclerosis in apolipoprotein E-deficient mice

“…Atherosclerotic lesion surface area also correlated with the serum cholesterol concentration in our study. van Exel et al 12 recently found a negative correlation between a low IL-10 production capacity of whole blood and total cholesterol level in humans. They speculated that high levels of IL-10 counteract the effects of TNF-a and IL-6 on lipid metabolism.…”

“…10,11 Despite the tremendous interest in the effects of cytokines on inflammation and lipoprotein metabolism, there have been few studies that have examined the influence of IL-10 on these processes in vivo. 12,13 As atherogenesis is a chronic process, the long-term expression of IL-10 is required in order to assess its effects on this disease. In this study, we have used adenoassociated virus (AAV) vectors for IL-10 gene transfer to investigate the antiatherosclerotic effects of IL-10 in vivo, because these vectors can transduce skeletal muscle and permit the sustained expression and systemic delivery of therapeutic proteins following a single intramuscular administration.…”

Inflammation and insulin resistance

“…Il-10 exerts its anti-inflammatory activity by inhibiting Tnf-induced NFjB activation by reducing IKK activity [38]. In human studies, it has been shown that there is a greater incidence of insulin resistance in subjects with reduced serum levels of IL-10 [39]. This raises the possibility that IL-10 might exert insulin-sensitizing effects.…”

Chemokines as risk factors for type 2 diabetes: results from the MONICA/KORA Augsburg study, 1984–2002

“…However, studies addressing the association of several immune mediators with type 2 diabetes in the same population indicate that there is no general upregulation of systemic immune mediator expression, but rather a specific and differential activation [5,7]. Data on IL-10 suggest that elevated expression of this cytokine in peripheral blood might even be protective against type 2 diabetes [8].…”