BACKGROUND: Intestinal transplantation provokes an intense inflammatory response within the graft muscularis that causes intestinal ileus. We hypothesised that endogenously produced anti-inflammatory substances could be utilised as novel therapeutics. Therefore, we tested the protective effects of inhaled @entity1223 (CO) and an endogenous @entity22456 ) anti-inflammatory mediator on transplant induced inflammatory responses and intestinal ileus in the @entity35 . METHODS: Gastrointestinal transit of non-absorbable @entity2823 labelled dextran and in vitro jejunal circular muscle contractions were measured in controls and syngeneic orthotopic transplanted animals with and without CO inhalation (250 ppm for 25 hours). Inflammatory mRNAs for @entity568 , @entity3426 , @entity5 necrosis factor alpha ( @entity1505 ), @entity1590 ( @entity1590 ), inducible @entity842 ( @entity1506 ), @entity4645 ( @entity4645 ), and @entity13358 were quantified by real time reverse transcriptase-polymerase chain reaction and @entity22456 by northern blot. Histochemical stains characterised neutrophil infiltration and enterocyte apoptosis. RESULTS: Transplantation delayed transit and suppressed jejunal circular muscle contractility. @entity8 was significantly improved by CO inhalation. Transplantation initiated a significant upregulation in @entity568 , @entity3426 , @entity1505 , @entity1590 , @entity1506 , @entity4645 , and @entity22456 mRNAs with the graft muscularis. CO inhalation significantly decreased expression of @entity568 , @entity3426 , @entity1506 , and @entity4645 mRNAs. CO also significantly decreased serum @entity3542 levels ( @entity1506 activity). CONCLUSIONS: CO inhalation significantly improved post-transplant motility and attenuated the inflammatory cytokine milieu in the syngeneic @entity35 transplant model. Thus clinically providing CO, the end product of the anti-inflammatory @entity22456 pathway, may prove to be an effective therapeutic adjunct for clinical small bowel transplantation.

Immunomodulatory effects of inhaled @entity1223 on XXXX syngeneic small bowel graft motility.

@entity8 :: ('MESH:D007674', 'Disease') :: ['Transplantation induced dysmotility'] @entity1223 :: ('MESH:D002248', 'Chemical') :: ['carbon monoxide'] @entity1506 :: ('24599(Tax:10116)', 'Gene') :: ['iNOS'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumour'] @entity13358 :: ('25325(Tax:10116)', 'Gene') :: ['IL-10'] @entity568 :: ('24498(Tax:10116)', 'Gene') :: ['interleukin (IL)-6', 'IL-6'] @entity3542 :: ('CHEBI:16301', 'Chemical') :: ['nitrite'] @entity1505 :: ('24835(Tax:10116)', 'Gene') :: ['TNF-alpha'] @entity22456 :: ('24451(Tax:10116)', 'Gene') :: ['haeme oxygenase 1 (HO-1', 'HO-1'] @entity2823 :: ('MESH:D016650', 'Chemical') :: ['FITC'] @entity842 :: ('MESH:D009569', 'Chemical') :: ['nitric oxide'] @entity3426 :: ('24494(Tax:10116)', 'Gene') :: ['IL-1beta'] @entity35 :: ('10116', 'Species') :: ['rat'] @entity4645 :: ('29527(Tax:10116)', 'Gene') :: ['cyclooxygenase 2', 'COX-2'] @entity1590 :: ('25464(Tax:10116)', 'Gene') :: ['ICAM-1', 'intercellular adhesion molecule 1']
@entity35 :: (10116,Species) :: ['rat']
