Treatment with an interleukin-1 receptor antagonist protein prolongs mouse islet allograft survival.
An interleukin-1 receptor antagonist protein was evaluated with regard to its efficacy in allogeneic and xenogeneic islet transplantation. Alloxan-induced diabetic C57BL/6 (H-2b) mice were transplanted under the kidney capsule with 500 C57BL/Ks (H-2d) mouse islets. Alzet osmotic pumps, which release their content over an 11- to 13-day period, were implanted subcutaneously for continuous infusion of interleukin-1 receptor antagonist protein (1.0, 5.0, 8.0 mg.kg-1 x day-1) or phosphate-buffered saline. Blood glucose determinations were performed every second or third day; at death, the islet-bearing kidneys were morphologically evaluated. Mice treated initially with the higher interleukin-1 receptor antagonist protein concentrations were followed for an additional period after cessation of the drug release to evaluate whether a transitory interleukin-1 receptor antagonist protein treatment would induce tolerance to the graft. All phosphate-buffered saline-treated mice were hyperglycemic 11 days after islet allotransplantation. Most of their grafts were heavily infiltrated with mononuclear cells. In the various interleukin-1 receptor antagonist protein-treated groups, 60-80% of the mice were normoglycemic after 11 days. Moreover, light microscopic examinations showed that most mice treated with interleukin-1 receptor antagonist protein had normal islet grafts or grafts infiltrated with only a few mononuclear cells. After interruption of interleukin-1 receptor antagonist protein infusion (8.0 mg.kg-1 x day-1), all animals developed hyperglycemia within 2-9 days. In xenogeneic experiments, 500-750 fetal porcine islet-like cell clusters were transplanted under the kidney capsule of normoglycemic C57BL/6 mice. These animals were treated either with interleukin-1 receptor antagonist protein (8.0 mg.kg-1 x day-1) or phosphate-buffered saline.(ABSTRACT TRUNCATED AT 250 WORDS)
Sandberg
J O
JO
Department of Medical Cell Biology, Uppsala University, Sweden.
Eizirik
D L
DL
Sandler
S
S
Tracey
D E
DE
Andersson
A
A
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology*; D007262:Infusions, Intravenous; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D016381:Islets of Langerhans Transplantation / Q000473:pathology / Q000502:physiology*; D007668:Kidney; D051379:Mice; D008810:Mice, Inbred C57BL; D012795:Sialoglycoproteins / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
D001786:Blood Glucose; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins