Macrophage migratory inhibitory factor (MIF) expression in acute graft-versus-host disease (GVHD) in allogeneic hemopoietic stem cell transplant recipients

Abstract

Summary:Graft-versus-host disease (GVHD) is a major complication after hemopoietic stem cell transplantation (HSCT), but its pathogenesis remains uncertain. Macrophage migratory inhibitory factor (MIF) is an important mediator in the allo-immune reaction during renal transplantation, yet its role in hemopoietic stem cell transplantation (HSCT) remains unexplored. This study investigated the potential role of MIF in acute graft-versus-host disease (aGVHD) following allogeneic HSCT. Forty-six randomly selected patients undergoing autologous or allogeneic HSCT were studied. Immunohistochemistry and in situ hybridization were performed to examine tissue MIF mRNA and protein expression on skin and colonic biopsy specimens. The associated T cell and macrophage activation was also studied by immunohistochemical studies. A semi-quantitative method was used to assess MIF staining, as well as T cell and macrophage staining. Serial blood samples were analyzed by ELISA for serum MIF levels. Immunohistochemistry and in situ hybridization performed in 15 skin and 19 colonic biopsies from 17 patients who developed moderate to severe aGVHD showed a significant increase in MIF mRNA and protein expression compared with normal controls (seven skin and five colonic biopsies). MIF was localized within the epidermis and the vascular area of skin, but diffusely expressed in the entire thickness of colon. Macrophage and T lymphocyte infiltration was confined to areas of strong MIF expression. Serial analysis by ELISA showed that only patients who developed aGVHD (n = 19) exhibited an increase (two-to three-fold) in serum MIF during HSCT, but not in the allogeneic HSCT recipients without aGVHD (n = 7) or those who received autologous HSCT (n = 8). In 14 out of 19 patients, serum MIF peaked before the onset of aGVHD. Local and systemic up-regulation of MIF expression is associated

Macrophage-migration inhibitory factor: role in inflammatory diseases and graft rejection

“…Increasing expression of MIF was observed in acute neonatal necrotizing enterocolitis [71]. Colitis in acute graft-versus-host disease (GVHD) was correlated with local upregulation of MIF [72].…”

Serum macrophage migration inhibitory factor (MIF) levels after allogeneic hematopoietic stem cell transplantation

“…Lo et al. , (2002) reported that dramatic increase in local MIF expression in aGVHD is associated with infiltration of activated T cells and macrophages in allo‐HSCT in humans.…”

“…, (2002) reported that dramatic increase in local MIF expression in aGVHD is associated with infiltration of activated T cells and macrophages in allo‐HSCT in humans. Moreover, they reported that serum MIF levels of aGVHD patients at the onset of clinical aGVHD were increased at least two to fourfolds, when compared with those of allo‐HSCT patients without aGVHD (Lo et al. , 2002).…”

Pathophysiological roles of macrophage migration inhibitory factor in gastrointestinal, hepatic, and pancreatic disorders

“…In this disease, macrophages and T cells infiltrating the mucosa were confined to areas of strong MIF expression. Lo et al 61 suggested that local upregulation of MIF expression was strongly correlated to the occurrence of colitis in acute GVHD.…”

“…60 Lo et al 61 reported that MIF was diffusely expressed in the entire thickness of the colon in patients with acute graft-versus-host disease (GVHD). In this disease, macrophages and T cells infiltrating the mucosa were confined to areas of strong MIF expression.…”