Serum Concentrations Of Macrophage Migration Inhibitory Factor Research Articles

Kinetics of Serum Macrophage Migration Inhibitory Factor (MIF) and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) in Allogeneic Stem Cell Transplantation.

Buckgrand. Graft-versus host disease (GVHD) is a major complication after hematopoietic stem cell transplantation (HSCT). Macrophage migration inhibitory factor (MIF) plays a pivotal role in systemic as well as local inflammatory and immune responses. Recent reports that MIF expression is up-regulated in the allo-immune reaction during renal transplantation. Otherwise, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane protein belong to the TNF family. The level of TRAIL expression in T cells as well as NK cells can be markedly up-regulated after cell activations. In this study we report that kinetics of serum level of MIF and TRAIL in GVHD patients before and after HSCT.Patients and Methods. Date randomly obtained from 16 patients (10 males and 6 females) who underwent allo-SCT for treatment of hematological malignancies at Hokkaido University Hospital during the period May 2001 to January 2005. All patients were informed consent of peripheral blood smpling. Eight patients were received conventional transplantation and the others were reduced intensity stem cell transplantation (RIST). Seven patients have HLA identical sibling donor, but the others were received unrelated donor. Twelve of the 16 patients was achieved acute GVHD (aGVHD), gradeIto IIin 8 patients. Twelve patients survived day 100 after allo-SCT, 9 of those 12 patients developed chronic GVHD(cGVHD). Serum MIF and TRAIL concentration were measured at various time points using enzyme-linked immunosorbent assays (ELISAs).Results. Serum MIF concentration analysis by ELISA showed that only patients who developed aGVHD significantly increased (two folds) before and after allo-SCT (avelage, from 7.34 ng/ml before allo-SCT to 14.7 ng/ml after allo-SCT, p=0.018). However, we could not detect any correlation of MIF levels and aGVHD severity, donor sources. On the other hand, serum TRAIL concentration analysis by ELISA showed that patients who developed aGVHD were not associated (avelage, from 458.6 pg/ml before allo-SCT to 484.12 pg/ml after allo-SCT, p=0.632). We could not detect association aGVHD severity, donor sources. However, peak titer in aGVHD patients tends to decrease in unrelated transplantation (related 580.86pg/ml, unrelated 415.59pg/ml, p=0.22). Interestingly, we showed that average serum TRAIL concentration before allo-SCT associated with aGVHD and cGVHD. Serum TRAIL concentration with aGVHD patients (n=12, 458.85pg/ml) was tended to increase than without aGVHD (n=4, 330.45pg/ml, P=0.063) and with cGVHD patients (n=9, 535.21pg/ml) was significantly increase without cGVHD patients (n=3, 282.0 ng/ml, P=0.007).Discussion. The present study demonstrated the kinetics of MIF and TRAIL. Systemic up-regulation of MIF expression is associated with the occurrence of aGVHD. This data suggested that MIF after allo-SCT might play a pathogenetic role in aGVHD. On the other hand, we suggested that high level of TRAIL before allo-SCT associated acute and cGVHD. Maybe we might be to estimate acute and cGVHD in examining TRAIL level before allo-SCT. In conclusion our data are the first to establish an association TRAIL and GVHD in allogeneic stem cell transplantation.

Blockade of macrophage migration inhibitory factor ameliorates experimental autoimmune myocarditis

Macrophage migration inhibitory factor (MIF) is a cytokine that plays a critical role in the regulation of macrophage effector functions and T-cell activation. However, its role in the pathogenesis of experimental autoimmune myocarditis (EAM) has remained unresolved. In this study, we studied the role of the MIF in EAM. We investigated the expression of MIF in EAM using enzyme-linked immunosorbent assay, Northern blotting, and immunohistochemistry. Moreover, a neutralizing antibody (Ab) to MIF was injected intraperitoneally from day 0 to 20 (experiment 1), or from day 13 to 19 (experiment 2), after the immunization. Disease severity was estimated by the macroscopic and microscopic findings for the heart, heart weight to body weight ratio, and cellular and humoral immune responses on day 21. Enhanced MIF protein and mRNA expression in the heart tissue and an elevated serum MIF concentration were confirmed in EAM. In experiment 1, the anti-MIF Ab treatment markedly inhibited the onset of EAM. Moreover, a significant reduction in disease severity was also achieved even after the delayed anti-MIF Ab treatment in experiment 2. Furthermore, we demonstrated that MIF blockade decreased the expression of VCAM-1, TNF-α, and IL-1β and the migration of T-cells and macrophages in the EAM heart. These results demonstrate an important role of MIF in the pathogenesis of EAM and suggest that MIF blockade may be a promising new strategy for the treatment of myocarditis.

Macrophage migration inhibitory factor evaluation compared with prostate specific antigen as a biomarker in patients with prostate carcinoma.

Cytokines are polypeptides that constitute a class of chemical mediator molecules that modulate cell growth by inducing specific target gene expression. The objective of this study was to evaluate the clinical usefulness of serum evaluation of the cytokine macrophage migration inhibitory factor (MIF) in patients undergoing routine prostate specific antigen (PSA) screening. In this preliminary, retrospective study, the authors report the development of an enzyme-linked immunosorbent assay (ELISA) for MIF determination in serum samples. A polymerase chain reaction (PCR)-based assay investigated associations between MIF expression and prostate carcinoma (CaP). The authors developed a relative quantitative reverse transcriptase-PCR assay to determine MIF mRNA amounts within laser-capture microscopy (LCM)-dissected prostate epithelial cells. A comparison of serum MIF levels and total PSA levels identified a positive correlation (correlation coefficient [r2] = 0.61; P < 0.001; n = 509 patients), suggesting an association between elevated serum concentrations of these proteins and CaP. A correlation of serum MIF levels with a diagnosis of CaP demonstrated that patients with a previous CaP diagnosis had significantly elevated serum MIF concentrations (mean +/- standard deviation, 6.8 +/- 0.87 ng/mL; P < 0.001). To associate altered serum MIF levels with MIF mRNA expression within prostate epithelial cells, LCM-dissected prostate epithelial cells (formalin fixed biopsies from three different patients) were used to determine MIF mRNA amounts by PCR analysis. On average, MIF mRNA amounts were 6.5 times higher in CaP epithelial cells that were invasive to the margin compared with MIF mRNA amounts in normal prostate epithelial cells within the same biopsy specimen. The ELISA data from the current study suggested an association between increased MIF expression and CaP and suggested that serum MIF concentration may serve as a prognostic marker for CaP.

Macrophage Migration Inhibitory Factor Is an Essential Immunoregulatory Cytokine in Atopic Dermatitis

Macrophage migration inhibitory factor (MIF) is one of the immunoregulatory cytokines involved in T-cell activation and delayed-type hypersensitivity. To elucidate involvement of this cytokine in the pathogenesis of atopic dermatitis (AD), we examined serum MIF concentrations of patients with AD and non-atopic normal healthy individuals. The mean serum MIF concentration of the AD patients (n= 36) was 36.4 ± 3.7 ng/ml (mean ± SEM), whereas that of the non-atopic dermatitis patients (n= 17) or healthy individuals (n= 61) were 13.1 ± 1.8 or 6.5 ± 0.45 ng/ml, respectively. Accordingly, immunohistochemistry of the inflammatory skin lesion of an AD patient demonstrated that MIF protein was diffusely expressed throughout the whole epidermal layer. After 4-week steroid ointment treatment, the MIF concentration decreased as clinical symptoms improved. The serum level of TNF-α was also decreased in parallel with that of MIF. Considering the T-cell dysfunction and disordered cytokine-network reported in AD, it was strongly suggested that MIF was a critical protein for immunoregulation in the pathophysiological mechanism of AD. In this context, MIF may become a useful laboratory parameter to comprehend the clinical course of the disease.