R. Orsenigo

Evidence that SMS 201-995 enhances the immunosuppressive effect of FK506

Somatostatin (SS) was originally described as a growth hormone release inhibiting factor synthesised in the hypothalamus. Recently, SS and its receptor (SSTR) have been demonstrated in lymphoid tissues and seem to play a regulatory, largely inhibitory, role in immune responses. The aim of the present study was to check the immunosuppressive effect of a SS derived peptide, the octreotide (SMS 201-995) and to verify whether this molecule acted synergistically with FK506. An immunosuppressive effect of SMS was observed on the proliferation of rat spleen cells induced in vitro, either by polyclonal mitogens such as PHA or by alloantigens. With PHA stimulation, 10(-14) M SMS significantly enhanced the immunosuppressive action of 0.00001 microg/ml FK506. The addition of SMS in MLR (10(-11)-10(-9)M) increased the antiproliferative effect of both 0.0001 microg/ml and 0.00001 microg/ml FK506. In consideration of the extremely low concentration of both drugs that was required to obtain a good immunosuppression in vitro, we verified the association of FK506 and SMS in vivo in an allogeneic skin graft model that used Lewis (Lew) rats as donors and Brown Norway (BN) rats as recipients. BN treated with 0.1 mg/kg FK506 and 0.5-10 microg/kg SMS showed a significant increase in mean skin allograft survival time when compared to either a monotherapy or control group. None of the animals died or showed signs of drug-related toxicity. In conclusion, a combined therapy of SMS and FK506, administered at lower dosages than those that are considered therapeutic, led to an effective immunosuppression without any undesirable side effects.

Transplantation of small bowel alone or with the liver in pigs : Use of peripheral blood lymphocytes in monitoring rejection

Abstract The small bowel is an organ with a large lymphoid component. In addition to the organized structures of the Peyers patches and mesenteric lymph nodes, the lamina propria also contains a vast mass of mobile lymphocytes. The transplantation of the small bowel has thus been associated with significant rejection phenomena and the possibility of graft-versus-host disease (GVHD) in the recipient, despite the immunosuppressive treatment. In a swine model, we have compared by mixed lymphocyte reaction (MLR) the immunological events occurring during orthotopic liver-small bowel transplantation (OLSBTx) and small bowel transplantation alone (SBTx) to evaluate a possible immunological advantage of combined liver-small bowel transplantation in order to prevent intestinal rejection.