Interleukin-6 and Interleukin-15 as Possible Biomarkers of the Risk of Autoimmune Diabetes Development.

Katarzyna Siewko,Danuta Lipinska,Natalia Wawrusiewicz-Kurylonek,Anna Zielinska-Maciulewska,Robert Milewski,Malgorzata Szelachowska,Piotr Szumowski,Adam Kretowski,Anna Poplawska-Kita,Maria Gorska,Rafal Maciulewski

doi:10.1155/2019/4734063

Abstract

Aim The aim of our study was to assay circulating interleukin-15 (IL-15) and interleukin-6 (IL-6) levels and insulin resistance measured by two different methods in newly diagnosed autoimmune diabetes (AD) patients, their I° relatives, and healthy controls. Material and Methods The group studied consisted of 54 patients with AD (28 with Latent Autoimmune Diabetes in Adults (LADA) and 26 with type 1 diabetes (T1D)), 70 first-degree relatives, and 60 controls. IL-6, IL-15, and anti-islet antibodies concentrations were measured by ELISA method. Homeostatic model assessment-insulin resistance (HOMAIR) and estimated glucose disposal rate (eGDR) were calculated. Results The patients with AD had significantly higher IL-15, IL-6, and HOMAIR and lower eGDR than the controls (p < 0.001, respectively) and first-degree relatives (p < 0.001, respectively). Significantly higher IL-15 and IL-6 were shown in the relatives with positive Ab as compared to the relatives without antibodies (p < 0.001, respectively) and the controls (p < 0.001, respectively). IL-15 negatively correlated with eGDR (r = −0.436, p = 0.021) in LADA and positively with HOMAIR in LADA and T1D (r = 0.507, p < 0.001; r = 0.4209, p < 0.001). Conclusions Significantly higher IL-15 and IL-6 concentrations, HOMAIR, and markedly lower eGDR in newly diagnosed AD patients and first-degree relatives with positive anti-islet antibodies might suggest the role of these pro-inflammatory cytokines and insulin resistance in the pathogenesis of autoimmune diabetes. IL-15 and IL-6 might be used as biomarkers of the risk of autoimmune diabetes development, in particular IL-15 for LADA. Both methods of IR measurement appear equally useful for calculating insulin resistance in autoimmune diabetes.

Highlights

Elevated circulating levels of pro-in ammatory peptides produced by mononuclear cells, observed in patients with AD, strongly suggest a role of a disturbed balance between pro-in ammatory cytokines, such as interleukin-1 (IL-1), interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α), and interferon-γ (IFN-γ), and those with anti-in ammatory properties, such as interleukin-4 (IL-4), interleukin-10 (IL-10), and tumor growth factor-β (TGF-β) in the pathogenesis of both types of autoimmune diabetes [4,5,6]
Our results demonstrated significantly higher concentrations of IL-15, IL-6, and Homeostatic model assessment-insulin resistance (HOMAIR) index as well as markedly lower estimated glucose disposal rate (eGDR) values in the patients with newly diagnosed AD, which may suggest the role of these pro-inflammatory cytokines and insulin resistance independent of weight in the pathogenesis of type 1 diabetes and latent autoimmune diabetes in adults (LADA)
Elevated concentrations of IL-15 and IL-6, lower eGDR value, and higher HOMAIR index found in the first-degree relatives with positive anti-islet antibodies suggest that serum IL-15 and IL-6 levels might be used as a biomarkers of AD risk and that insulin resistance could play a role in the prediabetic stage

Summary

Introduction

Elevated circulating levels of pro-in ammatory peptides produced by mononuclear cells, observed in patients with AD, strongly suggest a role of a disturbed balance between pro-in ammatory cytokines, such as interleukin-1 (IL-1), interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α), and interferon-γ (IFN-γ), and those with anti-in ammatory properties, such as interleukin-4 (IL-4), interleukin-10 (IL-10), and tumor growth factor-β (TGF-β) in the pathogenesis of both types of autoimmune diabetes [4,5,6]. Interleukin-6 and interleukin-15 are cytokines produced by monocytes/macrophages during innate and adaptive immune responses Both interleukins play an important role in the pathogenesis of several chronic autoimmune diseases: psoriasis, multiple sclerosis, rheumatoid arthritis, and ulcerative colitis. Some authors demonstrated an increased IL-6 concentration in T1D, while others found no differences in IL-6 concentrations between T1D patients and healthy controls, or even lower IL-6 concentration in T1D [14] In this light, the role of both cytokines in the pathogenesis of autoimmune diabetes seems still discursive

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Discussion

Conclusion