Effect of silica and carrageenan on the survival of islet allografts

Abstract

Pancreatic islet cell allotransplantation has considerable potential in the treatment of diabetes mellitus. However, isolated islets appear to be particularly sensitive to rejection and attempts to prolong their survival in experimental animals have so far met with only limited success. In this study the effect of two macrophage suppressing agents, silica and carrageenan, has been investigated in a rat model. Islets from (August x AS) F1 donors were transplanted into AS recipients. Of 13 animals treated with i.v. carrageenan (5 mg/kg), only one had prolongation of graft survival compared to controls. There was indefinite survival in 7 of the 16 animals treated with i.p. silica (50 mg/100 g) and 2 additional animals died normoglycaemic. In an attempt to measure the effectiveness of these two agents in suppressing macrophage activity, the ability of the "fixed" macrophages of the mononuclear phagocytic system to clear particles from the circulation was measured using 125I-labelled microaggregated albumin. Although both carrageenan and silica reduced clearance values, it proved impossible to correlate the degree and duration of this suppression with the success or otherwise of the islet cell allografts.