title: Administration of IL-1 trap prolongs survival of transplanted pancreatic islets to type 1 diabetic NOD mice.
abstract: We previously reported that IL-1 Trap (a hybrid molecule consisting of the extracellular domain of IL-1 receptor accessory protein and IL-1 receptor type 1 arranged inline and fused to the Fc-portion of IgG1) can protect rat pancreatic islets in vitro against noxious effects induced by IL-1β. In this study we tested the effect of administration of a murine IL-1 Trap on the recurrence of disease (ROD) model in non-obese diabetic (NOD) mice. Spontaneously diabetic female NOD mice received implantation of a curative number (600) of syngeneic pancreatic islets beneath their left kidney capsule from young healthy NOD mouse donors. Once a day, the mice were injected subcutaneously with IL-1 Trap (30mg/kg bodyweight), or an equimolar dose Fc-control protein (8.4mg/kg bodyweight) or saline. The treatments were maintained until ROD (i.e. a blood glucose value ⩾11.1mM for 2 consecutive days) or until 5days after transplantation. 3 out of 11 mice treated with IL-1 Trap showed a significantly increased graft survival compared to all other mice, and analysis of relative cytokine mRNA levels in isolated spleen cells showed elevated IL-4 mRNA levels, but no differences in FoxP3 or iNOS staining of grafts, from mice treated with IL-1 Trap, at both endpoints, compared to both control groups. Administration of IL-1 Trap counteracts islet cell destruction in the NOD mouse model of type 1 diabetes. In part this could be due to a shift towards Th2 cytokine production seen in IL-1 Trap treated animals.
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Biomedicum, P.O. Box 571, SE-75123 Uppsala, Sweden. Tobias.Rydgren@mcb.uu.se
authors.forename: Tobias
authors.initials: T
authors.lastname: Rydgren
authors.forename: Elin
authors.initials: E
authors.lastname: Öster
authors.forename: Monica
authors.initials: M
authors.lastname: Sandberg
authors.forename: Stellan
authors.initials: S
authors.lastname: Sandler
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental; D003922:Diabetes Mellitus, Type 1; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D006085:Graft Survival / Q000187:drug effects; D053577:Interleukin-1 Receptor Accessory Protein / Q000378:metabolism*; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation; D051379:Mice; D016688:Mice, Inbred NOD; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D053573:Receptors, Interleukin-1 Type I / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000378:metabolism
chemical_list: D001786:Blood Glucose; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053577:Interleukin-1 Receptor Accessory Protein; D012333:RNA, Messenger; D053573:Receptors, Interleukin-1 Type I; D011993:Recombinant Fusion Proteins; D015847:Interleukin-4; C531377:rilonacept; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II