Perioperative Infliximab Application Ameliorates Acute Rejection Associated Inflammation After Intestinal Transplantation

Abstract

As we have shown in the past, acute rejection-related TNF-a upregulation in resident macrophages in the tunica muscularis after small bowel transplantation (SBTx) results in local amplification of inflammation, decisively contributing to graft dysmotility. Therefore, the aim of this study is to investigate the effectiveness of the chimeric-monoclonal-anti-TNF-a antibody infliximab as perioperative single shot treatment addressing inflammatory processes during acute rejection early after transplantation. Orthotopic, isogenic and allogenic SBTx was performed in rats (

Gut Permeability and Glucose Absorption Are Affected at Early Stages of Graft Rejection in a Small Bowel Transplant Rat Model

“…27 These results validate previous reports, indicating that IFNg is a crucial driver of ACR in ITx. 28,29 One interesting finding of our experiments is the early loss of graft functional capacity as ACR progress. We used very simple techniques with tracers that could be easily translated to a clinical setup, such as glucose testing and OVA evaluation by ELISA.…”

Intestinal Regeneration, Residual Function and Immunological Priming Following Rescue Therapy After Rat Small Bowel Transplantation

“…Furthermore, we hypothesized that evaluation of molecular and cellular inflammatory responses, neural damage, histopathological integrity and functional assessment of the grafts in the recovery phase could identify the possible underlying mechanisms for chronic graft dysfunction after rescue therapy and subsequent graft recovery from ACR. Finally, we hypothesized that additional infliximab treatment could result in improved recovery and smooth muscle function through supplemental antiinflammatory effects as well as altered immune responses as suggested by a previous study (7). In summary, the objectives of this study were (1) to establish a standardized recovery model for the testing of different rescue therapy regimens, (2) to evaluate the process of recovery after acute rejection and to discover potential mechanisms for functional graft deterioration as well as immunological priming possibly inducing chronic rejection and (3) to assess the effects of anti-TNF-a therapy with infliximab as an additional component of a rescue strategy in the experimental setting.…”

Perioperative infliximab application has marginal effects on ischemia–reperfusion injury in experimental small bowel transplantation in rats

“…This leads to vasoconstriction, cytotoxicity, and induction of apoptosis in leukocytes and epithelial cells and to activation of signaling pathways resulting in increased transcription of many genes involved in inflammation, innate and adaptive immune response [8][9][10][11]. In a previous study, we evaluated perioperative infliximab application in our established model of experimental small bowel transplantation (SBTx) in rats [12]. The questionable effects of specific binding and inhibition of rat TNF-α by the humanized antibody infliximab have been extensively evaluated [12].…”

“…In a previous study, we evaluated perioperative infliximab application in our established model of experimental small bowel transplantation (SBTx) in rats [12]. The questionable effects of specific binding and inhibition of rat TNF-α by the humanized antibody infliximab have been extensively evaluated [12]. After allogenic transplantation, rats were treated with infliximab directly after reperfusion, while allogenic or isogenic transplanted animals without any treatment, nontransplanted animals, and intravenous immunoglobulin (IVIG)-treated animals served as controls.…”