title: Considerations for Defining Cytokine Dose, Duration, and Milieu That Are Appropriate for Modeling Chronic Low-Grade Inflammation in Type 2 Diabetes.
abstract: Proinflammatory cytokines have been implicated in the pathophysiology of both type 1 diabetes (T1D) and type 2 diabetes (T2D). T1D is an autoimmune disease involving the adaptive immune system responding to pancreatic beta-cells as antigen-presenting cells. This attracts immune cells that surround pancreatic islets (insulitis) and secrete cytokines, such as IL-1beta, IFN-gamma, and TNF-alpha, in close proximity to pancreatic beta-cells. In contrast, there is little evidence for such a focused autoimmune response in T2D. Instead, the innate immune system, which responds to cellular damage and pathogens, appears to play a key role. There are three major sources of proinflammatory cytokines that may impact islet/beta-cell function in T2D: (1) from islet cells, (2) from increased numbers of intraislet macrophages/immune cells, and (3) from increased circulating levels of proinflammatory cytokines due to obesity, presumably coming from inflamed adipose tissue. These differences between T1D and T2D are reflected by significant differences in the cytokine concentration, duration, and milieu. This review focuses on chronic versus acute cytokine action, cytokine concentrations, and cytokine milieu from the perspective of the pancreatic islet in T2D. We conclude that new cytokine models may be needed to reflect the pathophysiology of T2D more effectively than what are currently employed.
authors.affiliation: Diabetes Institute, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA; Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA.
authors.forename: Craig S
authors.identifier: 0000-0003-2894-3388
authors.initials: CS
authors.lastname: Nunemaker
mesh_terms: D000208:Acute Disease; D000273:Adipose Tissue / Q000276:immunology*; D002908:Chronic Disease; D016207:Cytokines / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007249:Inflammation / Q000276:immunology*; D007515:Islets of Langerhans / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008954:Models, Biological; D009765:Obesity / Q000276:immunology*; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: D016207:Cytokines