NK ACTIVITY DURING GRAFT-VERSUS-HOST DISEASE AND GRAFT-REJECTION IN RATS FOLLOWING INTESTINAL SEMIALLOGENIC AND ALLOGENIC TRANSPLANTATION WITH OR WITHOUT MESENTERIC LYMPHADENECTOMY

Graft-versus-host disease (GVHD) and graft rejection are major problems following intestinal transplantation (IT). Natural killer (NK) cells may be important effector cells in both conditions. In this study, Sprague-Dawley (SD) or SD-Brown Norway (BN) F1 rat intestine was transplanted into BN recipients with and without associated graft mesenteric lymphadenectomy (GML). Cyclosporine (15 mg/kg day) was administered to all animals. Pieces of the intestinal graft were examined 4 days posttransplant and again at death. NK activity calculated using intestinal intraepithelial lymphocytes (IL) was determined utilizing an 18-hr cytotoxic assay assessing 51Cr release and the results are reported as lytic units. YAC-1 cells were used as the target. NK activity was reduced 4 days after IT both in native (8.02 +/- 0.64) and in grafted bowel (3.14 +/- 1.51), with histological evidence of rejection as compared with that of control bowel in ungrafted rats (21.1 +/- 2.14). Survival was increased, on mean, a total of 6 days with the addition of GML in both semiallogenic and allogenic transplanted rats. At the time of death, the NK activity in the native bowel had increased (17.1 +/- 3.02) and histologic evidence of GVHD was present. These data suggest that: (1) NK cells are important in GVHD and (2) both semiallogenic and allogenic transplants survive longer if they are combined with GML (P < or = 0.05 and P < or = 0.01, respectively)

PARENTERAL ANTIBIOTICS AND SELECTIVE INTESTINAL DECONTAMINATION DO NOT PREVENT ENTERIC BACTERIAL OVERGROWTH OR TRANSLOCATION OBSERVED IN A SWINE MODEL OF SMALL-BOWEL TRANSPLANTATION

Alterations in the luminal microflora and increased intestinal translocation have been reported to occur following experimental and clinical small bowel transplantation (SET). Selective intestinal decontamination (SID) has been used to prevent luminal overgrowth and bacterial translocation. Despite the wide use of SID in clinical SET, there are no data supporting its usefulness in this situation. Thus, the aim of this investigation was to examine the effects of cyclosporine A (CSA) and SID upon bacterial overgrowth and translocation in a swine model of SET. Nineteen Large White female pigs weighing 30 +/- 2 kg underwent a total orthotopic SET and were randomly allocated to one of the following experimental groups as follows: Group 1 (No. 8) CSA 25 mg/kg body weight (b.w.)/day administered subcutaneously and Cefazolin 2 g/day im. Group 2 (No. 6) received the identical immunosuppression but the Cefazolin 2 g/day im was discontinued on the 5th Postoperative Day (pod) and switched to a SID regimen consisting of Vancomycin, 1 g, Nystatin, 500,000 IU, Colistin, 1,500,000 IU, and Tobramycin, 100 mg, given through a gastrostomy tube. Group 3 (No. 5) received no immunosuppression but antibiotic consisting of Cefazolin 2 g im/day. Group 4 (No. 7) underwent a small bowel autotransplantation. Group 4 received SID as in group 2 but no immunosuppression was given, Finally, 17 normal animals were sham-operated and were used as normal controls (N group). The animals in groups 1, 2, and 4 were sacrificed on the 29th pod. Those in group 3 were sacrificed on the 7th pod. Samples from graft, native bowel, liver, kidney, skin, and lungs were processed for histologic evaluation. Moreover, samples from the graft (proximal, middle, and distal) and adjacent mesenteric lymph nodes were harvested aseptically and cultured for both aerobes as well as for anaerobes. Significant increases in the number of aerobes and anaerobes were found in the proximal graft of all groups studied compared to the normal controls. The rate of intestinal translocation was 19% in the normal controls and increased to 88, 83, 100, and 100% in groups 1, 2, 3, and 4, respectively. Based upon these data, it can be concluded that SID is no better than a parenteral antibiotic regimen at preventing bacterial overgrowth following SET. Moreover, neither therapy reduces the high rate of bacterial translocation to mesenteric nodes seen in arrivals following experimental SET. (C) 1995 Academic Press, Inc