Bacterial translocation during graft-versus-host disease after small bowel transplantation is reduced following inhibition of inducible nitric oxide synthesis.
BACKGROUND
Increased nitric oxide (NO) production may contribute to intestinal barrier dysfunction and increased bacterial translocation (BT). Since BT may play a major role in graft-versus-host disease (GVHD) after small bowel transplantation (SBTx), we evaluated the role of NO production in GVHD after SBTX in the rat.


METHODS
Using the standard model of semiallogeneic SBTx in the rat, we prepared three experimental groups. Recipients in group 1 received LBNF1-LBNF1 transplants and were treated with aminoguanidine (AG) (200 mg/kg), recipients in group 2 received Lewis-LBNF1 grafts and were injected with saline, and recipients in group 3 received Lewis-LBNF1 transplants and AG (200 mg/kg). Urine nitrite/nitrate levels were measured daily, and BT was determined by culturing peritoneal swabs, mesenteric lymph nodes, spleen, liver, and blood.


RESULTS
In group 1 we detected indefinite survival with normal histology. In group 2 a survival of 10.5 +/- 1.1 days was reached, and the typical histological features of acute GVHD were observed. The animals in group 3 showed a mean survival of 14.8 +/- 0.6 days (P<0.02 compared with group 2) and the histological features of acute GVHD, although with a prolonged time course. Comparing NO production and BT between groups 2 and 3 we detected significantly reduced NO production on postoperative days 2-9 (P<0.03) and significantly decreased BT on postoperative days 3 and 9 (P<0.03).


CONCLUSIONS
Inhibition of inducible NO synthesis with AG reduces NO production, decreases BT, and prolongs survival during GVHD after SBTx and therefore may be a useful addition to standard treatment protocols for GVHD.
Langrehr
J M
JM
Department of Surgery, Charité Campus Virchow-Klinikum, Humboldt Universität zu Berlin, Germany. Jan.Langrehr@charite.de
Machens
C
C
Zill
E
E
Leder
K
K
Nüssler
A
A
Hoffman
R
R
Neuhaus
P
P
D000818:Animals; D018988:Bacterial Translocation / Q000187:drug effects*; D016207:Cytokines / Q000097:blood; D004731:Endotoxins / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006085:Graft Survival / Q000187:drug effects; D006086:Graft vs Host Disease / Q000097:blood / Q000382:microbiology* / Q000503:physiopathology / Q000652:urine; D006146:Guanidines / Q000494:pharmacology*; D007421:Intestine, Small / Q000473:pathology / Q000637:transplantation*; D008208:Lymphatic System / Q000473:pathology; D009566:Nitrates / Q000097:blood / Q000652:urine; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000097:blood / Q000652:urine; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D014184:Transplantation, Homologous
D016207:Cytokines; D004731:Endotoxins; D004791:Enzyme Inhibitors; D006146:Guanidines; D009566:Nitrates; D009573:Nitrites; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine