Serum Macrophage Migration Inhibitory Factor Levels Research Articles

Serum macrophage migration inhibitory factor levels in Hashimoto\u2019s thyroiditis

BackgroundHashimoto’s thyroiditis (HT) is the most common autoimmune thyroid disease. The actual mechanism by which the immunological factors lead to HT has remained obscure. Macrophage migration inhibitory factor (MIF) is recently recognized as a cytokine that has a broad range of inflammatory and immune effects. The aim of this study is to assess the role of MIF in the pathogenesis of HT.Patients and methodsOne hundred and twenty-nine patients were classified into three groups: (a) overt hypothyroidism, (b) subclinical hypothyroidism, and (c) the control group. A complete history taking, clinical examination, and laboratory investigations were done. Laboratory investigations included thyroid function tests [thyroid-stimulating hormone (TSH), triiodothyronine, and thyroxine], antithyroid antibodies (antithyroid peroxidase antibodies and thyroglobulin antibodies), and MIF level.ResultsThere is highly statistically significant difference between the three groups regarding MIF, the highest level being in group 1>group 2>group 3. In both hypothyroid groups (1 and 2), there are statistically significant positive correlations between MIF with TSH, thyroid peroxidase antibodies, and thyroglobulin antibodies, but there is no statistically significant correlation between MIF with thyroid functions tests and antithyroid antibodies in the control group.ConclusionSerum MIF levels increased in overt and subclinical hypothyroidism and its levels were positively correlated to TSH and thyroid-specific autoantibodies. Serum MIF levels play a role in the pathogenesis of thyroid autoimmune responses in patients with HT. We recommend further larger studies to assess the MIF role in the prognosis of the HT and its treatment by a new strategy.

Macrophage Migration Inhibitory Factor Levels in Gingival Crevicular Fluid, Saliva, and Serum of Chronic Periodontitis Patients.

Chronic periodontitis (CP) is an infection that affects the teeth supporting structure. Macrophage migration inhibitory factor (MIF) is an important effector cytokine of the innate immune system. Due to its functional characteristics, MIF may be involved in the immunopathology of CP. The aim of the present study was to evaluate MIF levels in gingival crevicular fluid (GCF), saliva, and serum of CP patients. A cross-sectional study was conducted on 60 subjects divided into two groups: subjects with CP (n= 30) and periodontally healthy subjects without CP (n=30). MIF was quantified in GCF, saliva, and serum of all participants by enzyme-linked immunosorbent assay. MIF concentrations were higher in GCF, saliva, and serum in the group with CP compared with the group without CP and a higher MIF concentration was observed in GCF (p=0.001) and saliva (p=0.009) in the group with CP. MIF intragroup comparisons between fluids demonstrated significant high levels of MIF in saliva compared with GCF and serum in both study groups (p<0.05). A positive correlation was found between clinical signs and MIF concentration in GCF (p<0.05). There is an association between the MIF and the clinical signs of the disease. Therefore, MIF could have an important role in the pathology and progression of CP.

Serum level of macrophage migration inhibitory factor predicts severity and prognosis in patients with ischemic stroke

ObjectiveTo evaluate whether the macrophage migration inhibitory factor (MIF) level in serum of ischemic stroke patients was associated with their clinical severity and early outcome. MethodsDuring February 2017–March 2018, consecutive patients admitted to our hospital because of first-ever ischemic stroke were identified. The prognostic value of MIF was set for predicting the outcome of these patients at discharge. The results were compared with existing methods, including National Institutes of Health Stroke Scale (NIHSS) score and validated indicators. Results289 patients were enrolled. The serum level of all patients was determined (median: 20.6 ng/ml). At admission, 131 patients (45.3%) were evaluated as minor stroke (NIHSS < 5). When serum level of MIF was increased by each 1 ng/ml, the unadjusted and adjusted risk of moderate-to-high clinical severity was elevated by 5% (OR = 1.05 [95% CI: 1.01–1.09], P = 0.006) and 3% (1.03 [1.00–1.08], P = 0.02), respectively. At discharge, 82 patients (28.4%) had poor functional outcomes. The median serum level of MIF was lower in group with good outcomes than that observed in poor outcomes (19.4[15.8–24.2] vs. 24.0[19.9–29.4] ng/ml; P < 0.001). When serum level of MIF was increased by each 1 ng/ml, the unadjusted and adjusted risk of poor outcomes was elevated by 9% (1.09 [1.05–1.13], P < 0.001) and 6% (1.06 [1.02–1.10], P < 0.01), respectively. ConclusionsHigh MIF levels are independently related to the moderate to high clinical severity in ischemic stroke patients, as well as the poor outcome at discharge.

The diagnostic value of macrophage migration inhibitory factor, carcinoembryonic antigen, and carbohydrate antigen 19-9 in gastric cancer

Introduction: Gastric cancer is a rather common malignancy worldwide and a major healthcare system issue. Lately, the importance of biomarkers such as macrophage migration inhibitory factor (MIF) has been demonstrated in the diagnosis of various gastrointestinal (GI) malignancies. The present study aimed to evaluate the diagnostic value of MIF, carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA 19-9) in gastric cancer. Methods: In this descriptive-analytical study, 84 patients with gastric cancer referred to the gastroenterology clinic of Tabriz University of Medical Sciences, Tabriz, Iran, for diagnostic and therapeutic procedures, and 80 healthy individuals were enrolled. Serum levels of MIF, CEA, and CA 19-9 were measured in both groups. Further, the grade and stage of the cancer were determined in in the patient group. Results: Serum levels of all three MIF, CEA, and CA 19-9 biomarkers in patients with gastric cancer were significantly higher than those of the control group (P = 0.001). However, no statistically significant correlations were found between the studied biomarkers with the tumor grade and stage. The MIF cut-off point for the diagnosis of gastric cancer was found to be 7.05 pg/ml and its sensitivity and specificity were 85.7% and 73.8%, respectively. Conclusion: MIF biomarker may involve in the pathogenesis and development of gastric cancer and it is a potential diagnostic and therapeutic marker in this malignancy.

The effect of abdominal Bevacizumab combined with hyperthermia chemotherapy on serum transforming growth factor beta 1 and migration-inhibitory factor levels in elderly patients with ovarian cancer

Objective To investigate the effect of abdominal Bevacizumab combined with hyperthermia chemotherapy on serum transforming growth factor beta1 (TGF-β1) and macrophage migration-inhibitory factor (MIF) levels in elderly patients with ovarian cancer. Methods A hundred elderly patients diagnosed with ovarian cancer from December 2011 to December 2014 at our hospital were recruited.Participants were assigned into a joint therapy group (n=50) and a thermal therapy group (n=50) according to the received treatment.Both groups were given the abdominal hyperthermia chemotherapy treatment, while the joint therapy group was additionally given Bevacizumab treatment.The effectiveness of treatment, adverse reactions, pre-and post-treatment serum TGF-β1 and MIF levels, and the 2-year survival situation in all participants were collected and analyzed. Results The therapeutic response rate and 2-year survival rate in the joint therapy group (64.0% and 60.0%) were significantly higher than those in the thermal therapy group (44.0% and 40.0%) (both P 0.05). Conclusions Abdominal Bevacizumab combined with hyperthermia chemotherapy can effectively decrease the levels of serum TGF-β1 and MIF in elderly patients with ovarian cancer and achieve improved short-term and long-term effectiveness with good safety. Key words: Ovarian cancer; Transforming growth factor beta1; Macrophage migration-inhibitory factors; Bevacizumab; Hyperthermia chemotherapy

MIF functional polymorphisms (-794 CATT5-8 and -173 G>C) are associated with MIF serum levels, severity and progression in male multiple sclerosis from western Mexican population

Macrophage migration inhibitory factor (MIF) is a cytokine associated with tissue damage in multiple autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and psoriatic arthritis. The role of MIF in multiple sclerosis (MS) and the contribution of its polymorphisms are unknown in our population. Therefore, we decided to investigate the genetic association of -794 CATT5-8 (rs5844572) and -173 G>C (rs755622) MIF polymorphisms with MS, clinical variables and MIF serum levels in the population of western Mexico. 230 MS patients diagnosed according to McDonald criteria and 248 control subjects (CS) were recruited for this study, both polymorphisms were genotyped by PCR and PCR-RFLP and MIF serum levels were measured by ELISA kit. Severity and progression of MS were evaluated by EDSS and MSSS scores, respectively. Genotypes carrying the 5 repeats alleles of -794 CATT5-8MIF polymorphism present higher MIF serum levels in comparison with no carriers, and the presence of 5,7 heterozygous genotype contribute to the increase of disease severity and damage progression in MS patients. Notably when we stratified by sex, an effect of risk alleles (7 repeats and -173*C) of both MIF polymorphisms on EDSS and MSSS scores on males was found (p < 0.01). This study suggests that polymorphic alleles of MIF polymorphisms could act as sex-specific disease modifiers that increase the severity and progression of MS in male Mexican-Mestizo western population.

Remote Ischemic Preconditioning Does Not Affect the Release of Humoral Factors in Propofol-Anesthetized Cardiac Surgery Patients: A Secondary Analysis of the RIPHeart Study

In contrast to several smaller studies, which demonstrate that remote ischemic preconditioning (RIPC) reduces myocardial injury in patients that undergo cardiovascular surgery, the RIPHeart study failed to demonstrate beneficial effects of troponin release and clinical outcome in propofol-anesthetized cardiac surgery patients. Therefore, we addressed the potential biochemical mechanisms triggered by RIPC. This is a predefined prospective sub-analysis of the randomized and controlled RIPHeart study in cardiac surgery patients (n = 40) that was recently published. Blood samples were drawn from patients prior to surgery, after RIPC of four cycles of 5 min arm ischemia/5 min reperfusion (n = 19) and the sham (n = 21) procedure, after connection to cardiopulmonary bypass (CPB), at the end of surgery, 24 h postoperatively, and 48 h postoperatively for the measurement of troponin T, macrophage migration inhibitory factor (MIF), stromal cell-derived factor 1 (CXCL12), IL-6, CXCL8, and IL-10. After RIPC, right atrial tissue samples were taken for the measurement of extracellular-signal regulated kinase (ERK1/2), protein kinase B (AKT), Glycogen synthase kinase 3 (GSK-3β), protein kinase C (PKCε), and MIF content. RIPC did not significantly reduce the troponin release when compared with the sham procedure. MIF serum levels intraoperatively increased, peaking at intensive care unit (ICU) admission (with an increase of 48.04%, p = 0.164 in RIPC; and 69.64%, p = 0.023 over the baseline in the sham procedure), and decreased back to the baseline 24 h after surgery, with no differences between the groups. In the right atrial tissue, MIF content decreased after RIPC (1.040 ± 1.032 Arbitrary units [au] in RIPC vs. 2.028 ± 1.631 [au] in the sham procedure, p < 0.05). CXCL12 serum levels increased significantly over the baseline at the end of surgery, with no differences between the groups. ERK1/2, AKT, GSK-3β, and PKCɛ phosphorylation in the right atrial samples were no different between the groups. No difference was found in IL-6, CXCL8, and IL10 serum levels between the groups. In this cohort of cardiac surgery patients that received propofol anesthesia, we could not show a release of potential mediators of signaling, nor an effect on the inflammatory response, nor an activation of well-established protein kinases after RIPC. Based on these data, we cannot exclude that confounding factors, such as propofol, may have interfered with RIPC.

Increased serum levels and promoter polymorphisms of macrophage migration inhibitory factor in schizophrenia

BackgroundNumerous studies have suggested that an immune system imbalance plays an important role in schizophrenia. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine. It plays multiple roles in various biological processes, including inflammation and neurogenesis. Furthermore, several exhaustive serum proteomic profiling studies have identified MIF as a potential biomarker of schizophrenia. Here, we investigate MIF protein levels in serum and postmortem prefrontal cortex in patients with schizophrenia and controls. Moreover, we investigate the association of two functional polymorphisms in the MIF gene promoter region (MIF-794CATT5–8 microsatellite and MIF-173G/C single-nucleotide polymorphism [SNP]) with schizophrenia. MethodsWe measured serum MIF levels with an enzyme-linked immunosorbent assay (ELISA) (51 patients vs. 86 controls) and postmortem brain MIF levels with a western blotting assay (18 patients vs. 22 controls). Subsequently, we genotyped the MIF-794CATT5–8 microsatellite with a fluorescence-based fragment assay and the MIF-173G/C SNP with a TaqMan SNP genotyping assay (1483 patients vs. 1454 controls). ResultsSerum MIF levels were significantly higher in patients with schizophrenia than in controls (p=0.00118), and were positively correlated with antipsychotic dose (Spearman's r=0.222, p=0.0402). In addition, an earlier age of onset was observed in patients with a high serum MIF level (≥40ng/mL) than those with a low serum MIF level (<40ng/mL) (p=0.0392). However, postmortem brain MIF levels did not differ between patients with schizophrenia and controls. The association study revealed that the CATT6-G haplotype was nominally significantly associated with schizophrenia (p=0.0338), and that the CATT6 allele and CATT6-G haplotype were significantly associated with female adolescent-onset schizophrenia (AsOS) (corrected p=0.0222 and p=0.0147, respectively). ConclusionsThese results suggest that serum MIF level is a potential pharmacodynamic and/or monitoring marker of schizophrenia, and is related to a novel antipsychotic effect beyond dopamine antagonism. Furthermore, the MIF gene polymorphisms are associated with the risk for schizophrenia especially in adolescent females, and are potential stratification markers of schizophrenia. Further studies of MIF are warranted to elucidate the pathophysiology of schizophrenia and the effects of antipsychotics.

Evaluation of macrophage migration inhibitory factor in patients with alopecia areata before and after the treatment

Background Alopecia areata (AA) is a common disease affecting the anagen phase of the hair follicles. It is considered as an autoimmune disorder. Many cytokines play a role in its pathogenesis; one of these cytokines is macrophage migration inhibitory factor (MIF). Aim The aim of this study was to evaluate the MIF level to elucidate its role in the pathogenesis of AA. Patients and methods This study included 50 patients with AA and 30 normal healthy individuals who served as the control group. Serum MIF levels were evaluated by enzyme-linked immunosorbent assay in patients (before and after the treatment) and in the controls. The clinical severity of the disease was done using severity of alopecia tool scoring system and it was correlated with the serum MIF levels. Results There was a statistically significant increase in the serum MIF level in patients before the treatment, compared to the controls. In addition to this, a significant elevation in its level was found before than found after the treatment. There was a positive significant correlation between the MIF level and both duration of the disease and its clinical severity, whereas there was a negative significant correlation between MIF level and the age of the patients. Conclusion Macrophage MIF plays an important role in the etiopathogenesis of AA as it is increased in patients when compared to the controls and in patients before than after the treatment. So, it could be considered as a prognostic factor for disease severity and might be a potential new target as a future therapy.

Salivary and Serum Markers Related to Innate Immunity in Generalized Aggressive Periodontitis.

Host inflammatory and immune responses play an important role in aggressive periodontitis (AgP). Thus, this study aims to evaluate levels of the innate immunity-related markers calprotectin, colony-stimulating factor (CSF)-1, macrophage migration inhibitory factor (MIF), monokine induced by interferon-γ (MIG), and matrix metalloproteinase (MMP)-8 in serum and saliva from patients with generalized AgP and those with gingivitis or a healthy periodontium. This study enrolled 40 individuals (17 males and 23 females; mean age 33.30 ± 9.31 years), 15 with generalized AgP, 15 with gingivitis, and 10 who were periodontally healthy. Full-mouth periodontal examinations were performed, and serum and saliva were collected. Levels of calprotectin, CSF-1, MIF, MIG, and MMP-8 were measured using enzyme-linked immunosorbent assays. In serum, mean levels of calprotectin were 2.06-fold higher in patients with AgP than in healthy patients (P = 0.01). Serum levels of MMP-8 were significantly elevated in patients with AgP compared with both healthy patients and those with gingivitis, by 2.60-fold and 2.77-fold, respectively (P = 0.03 and P = 0.009, respectively). In saliva, levels of MMP-8 were 5.66-fold higher in patients with AgP than in healthy patients (P = 0.02). CSF-1, MIF, and MIG levels in both serum and saliva did not differ significantly among the groups. Serum levels of calprotectin and MMP-8 are elevated in patients with AgP. MMP-8 levels are also increased in saliva from patients with AgP. These results support involvement of innate immune response in the pathogenesis of AgP.

Macrophage Migration Inhibitory Factor Predicts Outcome in Complex Aortic Surgery.

The perioperative inflammatory response is associated with outcome after complex aortic repair. Macrophage migration inhibitory factor (MIF) shows protective effects in ischemia-reperfusion (IR), but also adverse pro-inflammatory effects in acute inflammation, potentially leading to adverse outcome, which should be investigated in this trial. This prospective study enrolled 52 patients, of whom 29 (55.7%) underwent open repair (OR) and 23 (44.3%) underwent endovascular repair (ER) between 2014 and 2015. MIF serum levels were measured until 72 h post-operatively. We used linear mixed models and ROC analysis to analyze the MIF time-course and its diagnostic ability. Compared to ER, OR induced higher MIF release perioperatively; at 12 h after ICU admission, MIF levels were similar between groups. MIF course was significantly influenced by baseline MIF level (P = 0.0016) and acute physiology and chronic health evaluation (APACHE) II score (P = 0.0005). MIF level at 24 h after ICU admission showed good diagnostic value regarding patient survival [sensitivity, 80.0% (28.4–99.5%); specificity, 51.2% (35.1–67.1%); AUC, 0.688 (0.534–0.816)] and discharge modality [sensitivity, 87.5% (47.3–99.7%); specificity, 73.7% (56.9–86.6%), AUC, 0.789 (0.644–0.896)]. Increased perioperative MIF-levels are related to an increased risk of adverse outcome in complex aortic surgery and may represent a biomarker for risk stratification in complex aortic surgery.

Fenofibrate attenuates fatty acid-induced islet β-cell dysfunction and apoptosis via inhibiting the NF-κB/MIF dependent inflammatory pathway

BackgroundFatty acid-induced lipotoxicity and macrophage migration inhibitory factor (MIF) affect pancreatic β-cell function, and may promote the development of diabetes mellitus. However, the association of lipotoxicity with MIF and the effect of Fenofibrate on β-cell function remain unknown. MethodsLPL+/− mice and MIN6 cells stimulated with palmitic acid (PA) were utilized as models of lipid metabolism disorders. Factors associated with insulin secretion and apoptosis were assessed in the presence or absence of Fenofibrate. The possible mechanisms of lipotoxicity-induced β-cell dysfunction were also explored. ResultsFenofibrate effectively improved lipid accumulation in pancreatic β-cells, increased glucose-stimulated insulin secretion and β-cell mass, and significantly downregulated pro-apoptotic molecules, at the gene and protein levels, both in vivo and in vitro. Additionally, elevated MIF levels in serum from LPL+/− mice and PA-treated MIN6 cells were starkly decreased after Fenofibrate administration. Mechanistic analysis indicated that NF-κB signaling was remarkably triggered, which could further activate MIF transcription. Furthermore, Fenofibrate exerted beneficial effects on fatty acid-induced β-cell dysfunction likely by inhibiting the NF-κB/MIF dependent inflammatory response. ConclusionsFenofibrate ameliorates lipotoxicity-induced β-cell dysfunction and apoptosis by inhibiting the NF-κB/MIF inflammatory pathway. These findings provide novel insights into the treatment of lipotoxicity-induced metabolic disorders.

Macrophage Migration Inhibitory Factor Induces Inflammation and Predicts Spinal Progression in Ankylosing Spondylitis.

To investigate the role of macrophage migration inhibitory factor (MIF) in the pathogenesis of ankylosing spondylitis (AS). Patients who met the modified New York criteria for AS were recruited for the study. Healthy volunteers, rheumatoid arthritis patients, and osteoarthritis patients were included as controls. Based on the annual rate of increase in modified Stoke AS Spine Score (mSASSS), AS patients were classified as progressors or nonprogressors. MIF levels in serum and synovial fluid were quantitated by enzyme-linked immunosorbent assay. Predictors of AS progression were evaluated using logistic regression analysis. Immunohistochemical analysis of ileal tissue was performed to identify MIF-producing cells. Flow cytometry was used to identify MIF-producing subsets, expression patterns of the MIF receptor (CD74), and MIF-induced tumor necrosis factor (TNF) production in the peripheral blood. MIF-induced mineralization of osteoblast cells (SaOS-2) was analyzed by alizarin red S staining, and Western blotting was used to quantify active β-catenin levels. Baseline serum MIF levels were significantly elevated in AS patients compared to healthy controls and were found to independently predict AS progression. MIF levels were higher in the synovial fluid of AS patients, and MIF-producing macrophages and Paneth cells were enriched in their gut. MIF induced TNF production in monocytes, activated β-catenin in osteoblasts, and promoted the mineralization of osteoblasts. Our findings indicate an unexplored pathogenic role of MIF in AS and a link between inflammation and new bone formation.

Macrophage Migration Inhibitory Factor Serves As an Upstream Regulator of NLRP3 Expression and Subsequent IL-1beta Production in Human Monocytes in Response to Lupus U1-snRNP Immune Complex

Abstract The pathologic hallmarks of systemic lupus erythematosus (SLE or lupus) are altered immune responses to nuclear autoantigens with autoantibody production and subsequent tissue injury. TLR7/8 recognize the ssRNA of the self-antigen U1-small nuclear ribonucleorprotein (U1-snRNP) that is targeted by anti-U1-snRNP antibodies (Abs) in lupus. Recently, we showed IL-1β production from human monocytes (MO) exposed to a combination of U1-snRNP and anti-U1-snRNP Abs (snRNP immune complexes) via the NLRP3 inflammasome. Macrophage migration inhibitory factor (MIF), primarily produced from MO and macrophages, promotes the production of IL-1β, IL-6 and TNF-α, which are increased in lupus patients. Data showed an association between serum MIF levels and MIF gene polymorphisms with lupus-related organ damage and decreased glomerulonephritis in lupus-prone mice treated with MIF antagonists. Here we investigated the possible mechanisms underlying the functional link between MIF and the NLRP3 inflammasome. The snRNP immune complexes (ICs) induced high levels of MIF and IL-1β from freshly purified human MO. The small molecule MIF inhibitor MIF098, which interferes the binding of MIF to its receptor complex, decreased the production of IL-1β from MO in response to the snRNP ICs. The inhibitor substantially reduced the expression of NLRP3 and caspase-1 activation. This phenomenon is likely mediated in part by the suppression of NF-kB activation. Plus, exogenous MIF increased IL-1β production by the MO. Our results first show the production of MIF from MO by the lupus snRNP IC and the regulation of the NLRP3 inflammasome by MIF in human, providing a scientific rationale for translating animal studies targeting MIF into human lupus.

Association between the MIF-173G/C Polymorphism and Serum MIF levels with Pulmonary Tuberculosis: A Meta-analysis

Many studies have indicated that Macrophage migration inhibitory factor (MIF)-173G/C gene polymorphisms are associated with susceptibility to pulmonary tuberculosis (PTB). Additionally, some studies have suggested that there are higher levels of serum MIF in patients with PTB than the controls. However, the results of these studies were underpowered. The current study aimed to precisely evaluate the association between the MIF-173G/C polymorphism and serum MIF concentrations with PTB. Therefore, a systematic literature search was preformed to identify studies involving the indicated association. Eleven articles (1316 cases and 1272 controls) were included in the study. The results indicated that the MIF-173G/C polymorphism was significantly associated with PTB susceptibility, especially in Asians. Interestingly, the results further detected that circulating MIF levels were significantly higher in patients with PTB than in healthy controls, but this was only the case among Asians. Moreover, the statistical significance was also similar to that of the high quality group. The present study indicated that the MIF-173G/C polymorphism may contribute to the development of PTB. Furthermore, significantly higher serum MIF levels were observed in PTB patients than in controls, which further indicated that the MIF may play an important role in PTB progression, particularly in Asians.

Macrophage migration inhibitory factor siRNA inhibits hepatic metastases of colorectal cancer cells.

The purpose of this study was to assess the anti-tumor effects of macrophage migration inhibitory factor (MIF) siRNA on colorectal cancer in a mouse xenograft model. MIF specific siRNA (MIF siRNA) or a nonspecific control siRNA was introduced to murine colorectal cancer CT-26 cells. Mouse xenograft models of colorectal cancer were established. MIF siRNA, control siRNA or water was injected twice a week intravenously for 4 weeks. MIF siRNA inhibited the proliferation and migration, while induced apoptosis of CT-26 cells in vitro. Injection of MIF siRNA resulted in a significant decrease of serum MIF and VEGF levels, and the weight and volume of cecum-grafted tumors in vivo. In contrast, the number of apoptotic cells and caspase-3 expression were increased by MIF siRNA in cecum graft tumor tissues. Moreover, the water and fodder consumption were significantly improved by MIF siRNA treatment. Importantly, MIF siRNA reduced the hepatic metastases from colorectal cancer. Our results suggest that siRNA targeting MIF is a promising agent for the treatment of hepatic metastasis of colorectal cancer cells.

Voluntary running improves depressive behaviours and the structure of the hippocampus in rats: A possible impact of myokines

This study investigated the impact of voluntary exercise on depressive behaviours, serum and hippocampal levels of myokines, and histopathological features of hippocampal formation in rats. Depressed rats were allowed to voluntarily run on a wheel for 3weeks. Locomotor activity was assessed by a forced swimming test and the myokine levels in sera and hippocampal homogenates were measured using Enzyme-linked Immunosorbent Assay. Brain sections were analysed for hippocampal structure and neuronal counts. Voluntary running produced significant increase in the distance moved by rats and significant decrease in immobility duration. After voluntary running, there were significant increases in serum and hippocampal brain-derived neurotrophic factor (BDNF) and macrophage migration inhibitory factor (MIF), significant increase in hippocampal vascular endothelial growth factor (VEGF), and significant decrease in serum interleukin-6 (IL-6). Significant correlation was detected between the serum levels of BDNF and MIF (r=0.276) as well as IL-6 (r=−0.340). In addition, significant correlation was observed between hippocampal BDNF levels and MIF (r=0.500) and VEGF levels (r=0.279). After voluntary running, there was significant decrease in number degenerated neurons in hippocampal areas and significant increase in number of healthy neurons in the upper limb of the dentate gyrus, but not in its lower limb, compared to depression group. This study showed the relation of myokines to the development and/or relief of depression, as well as the correlation between serum and hippocampal myokine levels. Attention should be paid to studying the biological effects of myokines on different hippocampal areas that could respond differently to treatments.

Evaluation of macrophage migration inhibitory factor (MIF) levels in serum and lesional skin of patients with alopecia areata.

Alopecia areata (AA) is a non-scarring hair loss condition, the pathogenesis of which is not fully understood. Genetic predisposition, autoimmunity, and stress may each play a role. Macrophage migration inhibitory factor (MIF) is a cytokine that plays a role in the regulation of macrophage function. It also initiates inflammation and immune response by regulating a number of proinflammatory cytokines. This study was designed to study serum and lesional skin biopsy MIF levels in AA patients and to assess their associations with disease severity. This study included 30 patients with AA and 15 age- and sex-matched healthy control subjects. Quantitative measurements of MIF concentrations in sera and skin samples were obtained in both patients and control subjects. Associations with disease severity (assessed using the Severity of Alopecia Tool) were evaluated. Mean ± standard deviation (SD) MIF levels in serum and skin were significantly higher in AA patients (45.03 ± 26.98 ng/ml and 73.83 ± 29.81 ng/ml, respectively) than in controls (7.73 ± 1.62 ng/ml and 0.40 ± 1.12 ng/ml, respectively) (P < 0.01). Mean ± SD serum and skin MIF levels were also found to be higher in severe AA (69.93 ± 11.51 ng/ml and 100.80 ± 13.77 ng/ml, respectively) than in mild AA (20.13 ± 6.84 ng/ml and 46.87 ± 9.65 ng/ml, respectively) (P < 0.01). The finding that MIF is increased in serum and lesional skin of AA patients indicates its possible involvement in the pathogenesis of the disease.

Artesunate inhibits type I interferon-induced production of macrophage migration inhibitory factor in patients with systemic lupus erythematosus.

Macrophage migration inhibitory factor (MIF) is a key regulator of both atherosclerosis and systemic lupus erythematosus (SLE), yet factors leading to its overproduction remain unclear. To explore regulation of MIF in SLE, we studied effects and potential mechanisms of type I interferon (IFN) and artesunate (ART), an antimalarial agent extracted from Chinese herbs, on levels of MIF. Serum and peripheral blood cells from SLE patients and healthy controls were measured for MIF levels by ELISA and type I IFN-inducible gene expressions by real-time PCR, respectively, and assessed for associations by Spearman correlation. ART was added to human umbilical vein endothelial cell (HUVEC) cultures with or without prior IFNα-1b stimulation and to SLE peripheral blood mononuclear cell (PBMC) cultures. Protein levels of STATs and phosphorylated (p-) STATs in HUVECs were determined by Western blotting. Serum MIF levels were elevated in SLE patients and positively associated with disease activity (r = 0.86, p < 0.0001), accumulated damage (r = 0.34, p < 0.05), and IFN scores in SLE PBMCs (r = 0.74, p = 0.0002). The addition of IFNα-1b promoted MIF production in a time- and dose-dependent manner in HUVEC cultures. ART could inhibit expressions of IFN-inducible genes (LY6E and ISG15) in both HUVEC and SLE PBMC cultures, and suppress MIF production and over-expression of p-STAT1, but not p-STAT3 or STAT5, induced by IFNα-1b stimulation. IFNγ-induced expression of p-STAT1 in HUVECs was not inhibited by ART. MIF could be regulated by type I IFN in SLE patients. ART counteracts the effect of IFNα to inhibit MIF production by blocking STAT1 phosphorylation and thus may have therapeutic potential for SLE-associated atherosclerosis.

Synovial Fluid Macrophage Migration Inhibitory Factor Levels Correlate with Severity of Self-Reported Pain in Knee Osteoarthritis Patients

BackgroundInflammation is considered as one of the main pathogeneses in OA-induced pain. Macrophage migration inhibitory factor (MIF) is a well known pro-inflammatory cytokine. We aimed to determine whether MIF levels in serum and synovial fluid (SF) are associated with severity of OA-induced pain.Material/MethodsWe recruited 226 patients with knee OA and 106 controls. Self-reported pain severity of OA patients was evaluated using the Western Ontario McMaster University Osteoarthritis (WOMAC) pain scores. MIF levels were detected using enzyme-linked immunosorbent assay (ELISA).ResultsOA patients had similar serum MIF levels compared to controls (11.93 [5.68–18.10] vs. 10.06 [6.60–14.61] ng/ml, P>0.05). In OA patients, MIF levels in SF were dramatically lower compared to paired serum samples (3.39 [1.87–5.89] vs. 11.93 [5.68–18.10] ng/ml, P<0.01). MIF levels in SF were significantly correlated with WOMAC pain scores (r=0.237, P<0.001), but MIF levels in serum had no significant correlation with WOMAC pain scores (r=0.009, P=0.898).ConclusionsMIF levels in SF, but not in serum, were independently associated with the severity of self-reported pain in OA patients. The inhibition of MIF signaling pathways may be a novel therapeutic approach for ameliorating OA-induced pain.