Abstract
AimsInterleukin-22 (IL-22) has beneficial effects on body weight, insulin resistance and inflammation in different mouse models, but its relevance for the development of type 2 diabetes in humans is unknown. We aimed to identify correlates of serum IL-22 levels and to test the hypothesis that higher IL-22 levels are associated with lower diabetes incidence.MethodsCross-sectional associations between serum IL-22, cardiometabolic risk factors and glucose tolerance status were investigated in 1107 persons of the population-based KORA F4 study. The prospective association between serum IL-22 and incident type 2 diabetes was assessed in 504 initially non-diabetic study participants in both the KORA F4 study and its 7-year follow-up examination KORA FF4, 76 of whom developed diabetes.ResultsMale sex, current smoking, lower HDL cholesterol, lower estimated glomerular filtration rate and higher serum interleukin-1 receptor antagonist were associated with higher IL-22 levels after adjustment for confounders (all P < 0.05). Serum IL-22 showed no associations with glucose tolerance status, prediabetes or type 2 diabetes. Baseline serum IL-22 levels (median, 25th/75th percentiles) for incident type 2 diabetes cases and non-cases were 6.28 (1.95; 12.35) and 6.45 (1.95; 11.80) pg/ml, respectively (age and sex-adjusted P = 0.744). The age and sex-adjusted OR (95% CI) per doubling of IL-22 for incident type 2 diabetes of 1.02 (0.85; 1.23) was almost unchanged after consideration of further confounders.ConclusionsHigh serum levels of IL-22 were positively rather than inversely associated with several cardiometabolic risk factors. However, these associations did not translate into an increased risk for type 2 diabetes. Thus, our data argue against the utility of IL-22 as biomarker for prevalent or incident type 2 diabetes in humans, but identify potential determinants of IL-22 levels which merits further research in the context of cardiovascular diseases.
Highlights
Interleukin-22 (IL-22), a member of the IL-10 cytokine family, is produced by different leukocyte subsets and signals through a heterodimer of the IL-22 receptor 1(IL-22R1) paired with IL-10R2
Associations of serum IL‐22 levels with cardiometabolic risk factors In the cross-sectional analysis based on 1107 individuals, IL-22 serum levels were higher in men than in women and positively associated with age (Table 1)
In age and sexadjusted analyses, IL-22 serum levels were positively associated with BMI, fasting and 2-h insulin, HOMAIR, smoking status and circulating levels of IL-18, IL1RA and soluble intercellular adhesion molecule-1 (sICAM-1), but negatively with total cholesterol, HDL cholesterol and estimated glomerular filtration rate (Table 1)
Summary
While the latter is widely expressed, expression of IL-22R1 is restricted mainly to cell types in the pancreas and epithelial cells in liver, intestine, kidney and skin, which determines the specificity of IL-22 action [1, 2]. A recent study extended these data to metabolic disorders and found that mice lacking IL-22. Herder et al Cardiovasc Diabetol (2017) 16:17 signaling are prone to obesity and insulin resistance [4]. Several mouse models of obesity revealed beneficial effects of IL-22 treatment on glucose homeostasis, insulin sensitivity, insulin secretion and inflammation [4, 5]. Other studies have challenged the notion that IL-22 ameliorates insulin resistance and chronic inflammation in mice [6] or humans [7, 8]
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