title: Anakinra and tocilizumab enhance survival and function of human islets during culture: implications for clinical islet transplantation.
abstract: Pretreatment culture before islet transplantation represents a window of opportunity to ameliorate the proinflammatory profile expressed by human β-cells in duress. Anakinra (IL-1 receptor antagonist) and tocilizumab (monoclonal IL-6 receptor antibody) are two known anti-inflammatory agents successfully used in the treatment of inflammatory states like rheumatoid arthritis. Both compounds have also been shown to reduce blood glucose and glycosylated hemoglobin in diabetic patients. We therefore sought to evaluate the impact of anakinra and tocilizumab on human β-cells. The islets were precultured with or without anakinra or tocilizumab and then transplanted in a marginal mass model using human islets in immunodeficient mice. Islet viability was evaluated in an in vitro model. The pretreatment culture led to a significantly improved engraftment in treated islets compared to the vehicle. Anakinra and tocilizumab are not toxic to human islets and significantly reduce markers of inflammation and cell death. These results strongly support a pretreatment culture with anakinra and tocilizumab prior to human islet transplantation.
authors: Institute for Surgical Research, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors: Afaf
authors: A
authors: Sahraoui
authors: Kristine
authors: K
authors: Kloster-Jensen
authors: Thor
authors: T
authors: Ueland
authors: Olle
authors: O
authors: Korsgren
authors: Aksel
authors: A
authors: Foss
authors: Hanne
authors: H
authors: Scholz
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000628:therapy; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D051379:Mice; D016513:Mice, SCID
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; D053590:Interleukin 1 Receptor Antagonist Protein; C502936:tocilizumab