IL-6 is present in beta and alpha cells in human pancreatic islets: Expression is reduced in subjects with type 1 diabetes

• Published in: Clinical immunology (Orlando, Fla.) Vol. 211; p. 108320
• Main Authors: Rajendran, Sakthi, Anquetil, Florence, Quesada-Masachs, Estefania, Graef, Madeleine, Gonzalez, Nathaly, McArdle, Sara, Chu, Tiffany, Krogvold, Lars, Dahl-Jørgensen, Knut, von Herrath, Matthias
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2020
• ISSN: 1521-6616; 1521-7035; 1521-7035
• DOI: 10.1016/j.clim.2019.108320

IL-6 is a pro-inflammatory cytokine upregulated in some autoimmune diseases. The role of IL-6 in the development of type 1 diabetes (T1D) is unclear. Clinical studies are investigating whether tocilizumab (anti-IL-6 receptor) can help preserve beta cell function in patients recently diagnosed with T1D. However, in some rodent models and isolated human islets, IL-6 has been found to have a protective role for beta cells by reducing oxidative stress. Hence, we systematically investigated local tissue expression of IL-6 in human pancreas from non-diabetic, auto-antibody positive donors and donors with T1D and T2D. IL-6 was constitutively expressed by beta and alpha cells regardless of the disease state. However, expression of IL-6 was highly reduced in insulin-deficient islets of donors with T1D, and the expression was then mostly restricted to alpha cells. Our findings suggest that the implication of IL-6 in T1D pathogenesis might be more complex than previously assumed. •IL-6 is expressed on human pancreatic beta and alpha cells.•Beta cells are the source of majority of IL-6 in pancreatic islets.•IL-6 expression is reduced in islets of donors with type 1 diabetes, particularly in insulin-deficient islets.•IL-6 is secreted by live human islet cultures and increased upon metabolic and immune stress.