Ingested interferon-alpha prevents allograft islet transplant rejection

Ingested interferon (IFN)-alpha is a biological response modifier in experimental autoimmune encephalomyelitis and multiple sclerosis, and prevents type 1 diabetes in nonobese diabetic mice. Islet transplantation possesses significant potential advantages over whole-gland transplantation because it is simple, may achieve insulin independence, and has clear advantages over exogenous insulin therapy. Therefore, we examined whether ingested IFN-alpha, administered to islet allograft recipients, could prevent islet allograft rejection.

Recipient C3H mice (H2k) were made diabetic and either untreated or treated with 10-1000 international units (IU) of ingested murine IFN-alpha daily from day -7 through day +14 after transplantation for a total of 21 days. Seven days after diabetes induction, recipients received allograft islets isolated from C57BL.10 donors (H2b) under the kidney capsule and were followed for overt diabetes via elevated blood glucose.

Control recipients and recipients fed 1000 IU all became diabetic by day 13, whereas mice ingesting IFN-alpha had delayed rejection for up to 27 (10 IU) to 29 days (100 IU) after islet transplantation. Treatment of recipients of islet allografts with ingested IFN-alpha doubles the time period before rejection compared with control mice. The feeding period with daily IFN-alpha was doubled from 21 days to 42 days in total, 7 days before transplantation and 35 days after transplantation.

Treatment of recipients of islet allografts with prolonged ingested IFN-alpha prevents rejection in a subset of recipients. Ingested IFN-alpha may prevent rejection if given continuously after transplantation.