Increased Expression of Tissue Cytokines in Graft-Versus-Host Disease After Small Bowel Transplantation in the Rat1

Abstract

In conclusion, TNF-alpha, IFN-gamma, and IL-6 expression precede clinical onset and histologic evidence of GVHD in specific tissues. Therefore, increased expression of these cytokines is correlated with the development of GVHD in this model of SBT.

Inhibition of 5-lipoxygenase alleviates graft-versus-host disease

“…These chemokines drive the influx of leukocytes to GVHD target organs, contributing to the inflammatory response ( Serody et al, 2000 ; Terwey et al, 2005 ; Wysocki et al, 2005 ). Thus, our results showing the importance of reducing proinflammatory cytokine and chemokine levels in terms of prevention of fatal GVHD are in agreement with those of previous studies, which proposed an association between reducing the inflammatory response mediated by cytokines and chemokines and GVHD protection after experimental allogeneic hematopoietic stem cell transplant ( Piguet et al, 1987 ; Baker et al, 1996 ; Koide et al, 1997 ; Serody et al, 2000 ; Terwey et al, 2005 ; Wysocki et al, 2005 ; Castor et al, 2010 ; Schroeder and DiPersio, 2011 ; Robb and Hill, 2012 ). In addition, the reduced levels of the chemokines CCL2, CCL3, and CCL5 in zileuton-treated mice may also lead to reduced recruitment of inflammatory cells to target organs.…”

“…Thus, the reduction of CCL3 after 5-LO blockade may also be contributing to the reduction of CD4 and CD8 T cells in the target organs shown here. The proinflammatory cytokines IFN-γ and TNF are the major contributors to GVHD development ( Robb and Hill, 2012 ), and increased levels of these cytokines precede clinical GVHD signs ( Koide et al, 1997 ), including severe weight loss, diarrhea, skin changes, and high levels of mortality ( Piguet et al, 1987 ; Baker et al, 1996 ; Koide et al, 1997 ; Schroeder and DiPersio, 2011 ). Elevated levels of IFN-γ contribute to intestinal damage through direct cytotoxic effects and the activation of monocytes/macrophages to secrete lymphotoxins and TNF, enhancing organ damage ( Robb and Hill, 2012 ).…”

Lithothamnion muelleri Controls Inflammatory Responses, Target Organ Injury and Lethality Associated with Graft-versus-Host Disease in Mice

“…IFN-γ and TNF-α are well-known to have relevant roles in GVHD [19]. Increased levels of these cytokines precede clinical GVHD symptoms and are associated with a systemic syndrome of weight loss, diarrhea, skin changes, and high mortality [39,40,41,42]. We also observed increased levels of these cytokines at day 10 after transplantation in GVHD mice; this finding coincided with the onset of clinical disease and subsequent mortality as seen below.…”