Migration Inhibitory Factor Levels Research Articles

Neuroinflammatory CSF biomarkers MIF, sTREM1, and sTREM2 show dynamic expression profiles in Alzheimer’s disease

BackgroundThere is a need for novel fluid biomarkers tracking neuroinflammatory responses in Alzheimer’s disease (AD). Our recent cerebrospinal fluid (CSF) proteomics study revealed that migration inhibitory factor (MIF) and soluble triggering receptor expressed on myeloid cells 1 (sTREM1) increased along the AD continuum. We aimed to assess the potential use of these proteins, in addition to sTREM2, as CSF biomarkers to monitor inflammatory processes in AD.MethodsWe included cognitively unimpaired controls (n = 67, 63 ± 9 years, 24% females, all amyloid negative), patients with mild cognitive impairment (MCI; n = 92, 65 ± 7 years, 47% females, 65% amyloid positive), AD (n = 38, 67 ± 6 years, 8% females, all amyloid positive), and DLB (n = 50, 67 ± 6 years, 5% females, 54% amyloid positive). MIF, sTREM1, and sTREM2 levels were measured by validated immunoassays. Differences in protein levels between groups were tested with analysis of covariance (corrected for age and sex). Spearman correlation analysis was performed to evaluate the association between these neuroinflammatory markers with AD-CSF biomarkers (Aβ42, tTau, pTau) and mini-mental state examination (MMSE) scores.ResultsMIF levels were increased in MCI (p < 0.01), AD (p < 0.05), and DLB (p > 0.05) compared to controls. Levels of sTREM1 were specifically increased in AD compared to controls (p < 0.01), MCI (p < 0.05), and DLB patients (p > 0.05), while sTREM2 levels were increased specifically in MCI compared to all other groups (all p < 0.001). Neuroinflammatory proteins were highly correlated with CSF pTau levels (MIF: all groups; sTREM1: MCI, AD and DLB; sTREM2: controls, MCI and DLB). Correlations with MMSE scores were observed in specific clinical groups (MIF in controls, sTREM1 in AD, and sTREM2 in DLB).ConclusionInflammatory-related proteins show diverse expression profiles along different AD stages, with increased protein levels in the MCI stage (MIF and sTREM2) and AD stage (MIF and sTREM1). The associations of these inflammatory markers primarily with CSF pTau levels indicate an intertwined relationship between tau pathology and inflammation. These neuroinflammatory markers might be useful in clinical trials to capture dynamics in inflammatory responses or monitor drug–target engagement of inflammatory modulators.

MIF in the cerebrospinal fluid is decreased during relapsing-remitting while increased in secondary progressive multiple sclerosis

BackgroundMacrophage migration inhibitory factor (MIF) is involved in the function of both the innate and adaptive immune systems and in neuroprotection and has recently been implicated in multiple sclerosis (MS). ObjectivesDetermination of MIF levels in the cerebrospinal fluid (CSF) of patients with distinct subtypes of MS and the cellular localization of MIF in human brain tissue. MethodsThe levels of MIF were investigated in CSF from patients with clinically isolated syndrome (CIS) (n = 26), relapsing-remitting MS (RRMS) (n = 22), secondary progressive MS (SPMS) (n = 19), and healthy controls (HCs) (n = 24), using ELISA. The effect of disease-modifying therapies in the RRMS and SPMS cohorts were examined. Cellular distribution of MIF in the human brain was studied using immunochemistry and the newly available OligoInternode database. ResultsMIF was significantly decreased in treatment-naïve CIS and RRMS patients compared to HCs but was elevated in SPMS. Interestingly, MIF levels were sex-dependent and significantly lower in women with CIS and RRMS. MIF expression in the human brain was localized to neurons, astrocytes, pericytes, and oligo5 oligodendrocytes but not in microglia. ConclusionThe finding that MIF was decreased in newly diagnosed CIS and RRMS patients but was high in patients with SPMS may suggest that MIF levels in CSF are regulated by local MIF receptor expression that affects the overall MIF signaling in the brain and may represent a protective mechanism that eventually fails.

MIF/SCL3A2 depletion inhibits the proliferation and metastasis of colorectal cancer cells via the AKT/GSK-3β pathway and cell iron death.

This study investigated the mechanisms of migration inhibitory factor (MIF) and solute carrier family 3 member 2 (SLC3A2) in colorectal cancer progression. The levels of MIF and SLC3A2 expression in cells were measured by RT‐qPCR. SW480 and SW620 cells were transfected with sh‐MIF and sh‐SLC3A2, respectively. MIF, SLC3A2, GPX4, E‐cadherin and N‐cadherin expression were detected by immunofluorescence (IF). CCK8 and Transwell assays were performed to detect cell proliferation and migration. Co‐immunoprecipitation (CoIP) was used to measure the binding activity of MIF and SLC3A2. Finally, a nude mouse tumorigenicity assay was used to confirm the functions of MIF and SLC3A2 in colorectal cancer. Results showed that the levels of MIF and SLC3A2 expression were up‐regulated in colorectal cancer cells. Inhibition of MIF or SLC3A2 expression prevented cell proliferation, migration, epithelial‐mesenchymal transition (EMT) and invasion. In addition, knockdown of MIF and SLC3A2 promoted iron death in SW480 and SW620 cells. CoIP results showed that MIF and SLC3A2 directly interact with each other. Knockdown of both MIF and SLC3A2 inhibited tumour growth and metastasis via the AKT/GSK‐3β pathway in vivo. The Akt/GSK‐3β pathway was found to participate in regulating MIF and SLC3A2 both in vivo and in vitro. MIF and SLC3A2 might be potential biomarkers for monitoring the treatment of colorectal cancer.

Evaluation of Macrophage Migration Inhibitory Factor (MIF) Level as a Biomarker for Rheumatoid Arthritis among Iraqi Patients

Rheumatoid arthritis (RA) is a common chronic inflammatory autoimmune disease. MIF protein is one of proinflammatory cytokines has been implicated in various inflammatory and immune-mediated diseases. Therefore, the goal of the study was to assess the role of MIF in the pathogenesis of RA in Iraqi patient. One hundred and eighty (180) participants were involved; ninety patients with RA and ninety healthy controls. All participants were assessed by the following diagnostic lab analyses: RF, Anti-CCP, ESR, CRP and CBC to confirm RA disease. MIF level were evaluated in participants' sera by using ELISA assay. The age mean of RA patients was (52.03 ± 13.01); the patients more than 50 years age represent 57.80%. Significant difference was recorded in male and female frequencies among patients and controls (p=0.023). The mean of RA patients' body weight was (83.68 ± 14.15). According to disease duration, more than 10 years of disease duration was the most frequent (44.4%). Disease activity score recorded that (55.6%) of patients represent a moderate RA activity. Median levels of RF, CRP, Anti-CCP Abs and ESR recorded a significant increase in RA patients' sera; RBCs and HGB recorded lower values in patients of RA compared to control group; WBCs, lymphocyte and PLT count recorded no significant differences between the study groups (p-value&gt;0.05 for all), while significant high value of neutrophils was recorded in RA patients than in healthy control (p&lt;0.001). The mean of MIF serum level showed significant increase in RA patients compared to controls (22.51 vs. 4.33 ng/ml; p&lt; 0.001); receiver operator characteristics curve (ROC) of MIF indicated that MIF was a predictor of RA. Patients at the age group (20 – 29 years) showed a significant increased mean of MIF level compared to other age groups of patients; no significant differences between MIF level and disease activity score in RA patients. In conclusion, MIF is an important biomarker for RA that may have a role in the pathogenesis of this disease.

Novel CSF inflammatory markers MIF and TREM‐1 are increased in Alzheimer’s disease

AbstractBackgroundThere is a lack of biomarkers reflecting Alzheimer‐relevant pathological processes such as inflammation, to improve Alzheimer’s differential diagnosis. Our recent discovery cerebrospinal fluid (CSF) proteomics study, revealed potential AD‐specific biomarkers related to inflammatory pathology, such as migration inhibitory factor (MIF) and triggering receptor expressed on myeloid cells 1 (TREM‐1). Here, we aimed to validate these findings including also samples from patients with dementia with Lewy Body (DLB) using a novel sensitive technology purposed for clinical implementation.MethodMIF and TREM‐1 levels were measured in CSF from patients with AD (n=38, 66 ± 6 years, 97% males), DLB (MIF: n=50, TREM‐1: n=40, 67 ± 7 years, 95% males) and controls (cognitively unimpaired, n=37, 66 ± 6 years, 95% males) using assays on the antibody‐based SimplePlex technology, in‐house validated for CSF analysis. Differences in protein levels between diagnostic groups and correlations to AD CSF biomarkers and mini‐mental state examination (MMSE) scores were tested by analysis of covariance (corrected for age and sex) and Spearman correlations. An optimal prediction panel was identified using backward elimination logistic regression analysis with likelihood ratio and ROC analyses.ResultCSF MIF levels were increased in AD (1.2‐fold, p=0.002) and DLB (1.14‐fold, p=0.036) compared to controls (figure 1A). MIF levels correlated with total‐ and phosphorylated‐Tau (t‐Tau, ρ=0.670, p&lt;0.001; p‐Tau, ρ=0.686 p&lt;0.001) and Amyloid‐beta 42 (Aβ42, ρ=‐0.189, p&lt;0.05) but not with MMSE (p&gt;0.05). CSF TREM‐1 levels were increased in AD compared to DLB (1.4‐fold, p=0.016) and controls (1.5‐fold, p=0.003, figure 1B) and correlated with all three AD CSF biomarkers (t‐Tau: ρ =0.472, p=0.001; p‐Tau: ρ=0.414, p=0.001; Aβ42: ρ=‐0.267, p=0.018) but not with MMSE (p&gt;0.05). A panel combining MIF, t‐Tau and p‐Tau differentiated AD from DLB with high accuracy (AUC=0.941 (95%CI: 0.892‐0.989, 88% sensitivity, 89% specificity, figure 2).ConclusionInflammatory‐related proteins MIF and TREM‐1 are increased in AD. We here validated previous proteomics findings in an independent cohort using a technology that is used as a first preparatory step towards clinical implementation. This data highlights the importance of biomarkers reflecting different pathological processes as these proteins could be used to provide insight into an ongoing neuroinflammatory response.

Inflammatory cytokines associated with outcomes in orthopedic trauma patients independent of New Injury Severity score: A pilot prospective cohort study.

Traumatic injury is the leading cause of mortality in patients under 50. It is associated with a complex inflammatory response involving hormonal, immunologic, and metabolic mediators. The marked elevation of cytokines and inflammatory mediators subsequently correlates with the development of posttraumatic complications. The aim was to determine whether elevated cytokine levels provide a predictive value for orthopedic trauma patients. A prospective cohort study of patients with New Injury Severity Score (NISS) > 5 was undertaken. IL-6, IL-8, IL-10, and migration inhibitory factor levels were measured within 24-h of presentation. Demographic covariates and clinical outcomes were obtained from the medical records. Fifty-eight patients (83% male, 40 years) were included. Addition of IL-6 to baseline models significantly improved prediction of pulmonary complication (LR = 6.21, p = 0.01), ICU (change in R2 = 0.31, p < 0.01), and hospital length of stay (change in R2 = 0.16, p < 0.01). The addition of IL-8 significantly improved the prediction of acute kidney injury (LR = 9.15, p < 0.01). The addition of postinjury IL-6 level to baseline New Injury Severity Score model is better able to predict the occurrence of pulmonary complications as well as prolonged ICU and hospital length of stay.

Preoperative Serum Macrophage Migration Inhibitory Factor Level Correlates with Surgical Difficulty and Outcome in Patients with Autoimmune Thyroiditis.

Surgical treatment for autoimmune thyroid disease is theoretically risky due to its chronic inflammatory status. This study aimed to investigate the correlation between preoperative serum migration inhibitory factor (MIF) levels and the difficulty of thyroidectomy in patients with autoimmune thyroiditis. Forty-four patients (average age: 54 years) were prospectively recruited: 30 with autoimmune thyroiditis and 14 with nodular goiter. Preoperative serum samples were collected to measure MIF levels. The difficulty of thyroidectomy was evaluated using a 20-point thyroidectomy difficulty scale (TDS) scoring system. The potential correlations between MIF levels and clinicopathological features as well as postoperative complications were analyzed. Preoperative serum thyroid-stimulating hormone (TSH), TSH receptor antibody, thyroid peroxidase antibodies levels, TDS score, and serum MIF levels were significantly higher in the autoimmune thyroiditis group than those in the goiter group. MIF levels were significantly associated with postoperative transient recurrent laryngeal nerve injury and hypoparathyroidism. MIF levels were positively correlated with TDS score, operation time, and blood loss in the autoimmune thyroiditis group. Increased preoperative serum MIF levels are associated with higher TDS scores, operation time, blood loss, and postoperative complications. Preoperative serum MIF level may be a useful predictor of difficult thyroidectomy and help surgeons provide better preoperative management.

Evaluation of the relationship between macrophage migration inhibitory factor level and clinical course in patients with COVID‐19 pneumonia

The COVID‐19 pandemic, which has ravaged our world for more than a year, still shapes our agenda with a scale of intensity that fluctuates over time. In our study, we aimed to determine the correlation between serum migration inhibitory factor (MIF) level and disease severity in COVID‐19 with different prognoses. Between 15 October 2020 and 20 January 2021, 110 patients over the age of 18 who were diagnosed with COVID‐19 and 40 volunteer healthcare personnel were included in our study. MIF levels were measured by enzyme‐linked immunosorbent assay. In the comparison of serum MIF values in the patient and control group, it was observed that the MIF level was significantly higher in patients with both moderate and severe COVID‐19 levels compared to the control group (p = 0.001, 0.001). In the comparison of serum MIF values of moderate to severe COVID‐19 patients, it was observed that MIF level was higher in severe patients (p = 0.001). In the receiver operating characteristic curve analysis performed to differentiate between severe and moderate COVID‐19 patients with MIF levels, the area under the curve was observed as 0.78. When the cutoff value of the MIF level was taken as 4.455 ng/ml, the sensitivity was 83% and the specificity was 62%. Failure to adequately balance the pro‐inflammatory cytokines synthesized in COVID‐19 with anti‐inflammatory effect is the most important reason for the aggravation of the disease course. Playing a role in pro‐inflammatory cytokine synthesis, MIF can provide important information about the disease prognosis in the early period.

Balance between macrophage migration inhibitory factor and sCD74 predicts outcome in patients with acute decompensation of cirrhosis

Background & AimsMacrophage migration inhibitory factor (MIF) is an inflammatory cytokine and an important regulator of innate immune responses. We hypothesised that serum concentrations of MIF are associated with disease severity and outcome in patients with decompensated cirrhosis and acute-on-chronic liver failure (ACLF).MethodsCirculating concentrations of MIF and its soluble receptor CD74 (sCD74) were determined in sera from 292 patients with acute decompensation of cirrhosis defined as new onset or worsening of ascites requiring hospitalisation. Of those, 78 (27%) had ACLF. Short-term mortality was assessed 90 days after inclusion.ResultsAlthough serum concentrations of MIF and sCD74 did not correlate with liver function parameters or ACLF, higher MIF (optimum cut-off >2.3 ng/ml) and lower concentrations of sCD74 (optimum cut-off <66.5 ng/ml) both indicated poorer 90-day transplant-free survival in univariate analyses (unadjusted hazard ratio [HR] 2.01 [1.26–3.22]; p = 0.004 for MIF; HR 0.59 [0.38–0.92]; p = 0.02 for sCD74) and after adjustment in multivariable models. Higher MIF concentrations correlated with surrogates of systemic inflammation (white blood cells, p = 0.005; C-reactive protein, p = 0.05) and were independent of genetic MIF promoter polymorphisms. Assessment of MIF plasma concentrations in portal venous blood and matched blood samples from the right atrium in a second cohort of patients undergoing transjugular intrahepatic portosystemic shunt insertion revealed a transhepatic MIF gradient with higher concentrations in the right atrial blood.ConclusionsSerum concentrations of MIF and its soluble receptor CD74 predict 90-day transplant-free survival in patients with acute decompensation of cirrhosis. This effect was independent of liver function and genetic predispositions, but rather reflected systemic inflammation. Therefore, MIF and sCD74 represent promising prognostic markers beyond classical scoring systems in patients at risk of ACLF.Lay summaryInflammatory processes contribute to the increased risk of death in patients with cirrhosis and ascites. We show that patients with high serum levels of the inflammatory cytokine macrophage migration inhibitory factor (MIF) alongside low levels of its binding receptor sCD74 in blood indicate an increased mortality risk in patients with ascites. The cirrhotic liver is a relevant source of elevated circulating MIF levels.

Expression profile of macrophage migration inhibitory factor in periodontitis

ObjectiveMacrophage migration inhibitory factor (MIF) is a pivotal mediator of host innate immunity and influences the development of several inflammatory diseases. The role of MIF in periodontitis is unclear. MethodsEighteen periodontally healthy volunteers and 18 patients with stage III or IV periodontitis were enrolled. Blood samples and gingival tissues were collected from all individuals. The serum concentrations of MIF and MCP-1 were measured by ELISA. The protein and mRNA levels of MIF and MCP-1 in gingival tissue were evaluated by immunohistochemical staining and quantitative PCR. The levels of secreted MIF and MCP-1, as well as their mRNA levels, were determined by ELISA and quantitative PCR in oral epithelial cells infected with Porphyromonas gingivalis. ResultsAfter adjusting for age, the level of MCP-1 was significantly higher in the serum and gingival tissue of periodontitis patients, as well as in infected epithelial cells. The serum concentration of MIF was increased in periodontitis patients (15.25 ± 2.16 ng/mL, P < 0.05) compared to healthy controls (10.43 ± 1.02 ng/mL). Increased MIF immunoreactivity was found in gingival epithelial tissue but not in the gingival connective tissue of periodontitis patients. The secretion of MIF was 3.82-fold higher in the supernatant of infected cells than in the supernatant of control (P < 0.01). No increase in the MIF mRNA level was found in either gingival tissue or epithelial cells. ConclusionsBased on our limited evidence, we showed the level of MIF was related to periodontal conditions. P. gingivalis may contribute to the development and progression of periodontitis through MIF.

Migration inhibitory factor in spinal tuberculosis: -173G/C polymorphisms, and transcript and protein levels in a northern province of China.

The aim of this study was to elucidate the possible association between migration inhibitory factor (MIF)-173G/C gene polymorphisms and transcript and plasma levels of MIF in spinal tuberculosis (TB) patients. Clinical data were collected from 254 spinal TB patients and 262 healthy controls participating in the study. The genotype of the MIF-173G/C gene was amplified by polymerase chain reaction and genotyped by DNA sequencing technology. The level of mRNA expression was determined by real-time polymerase chain reaction and MIF plasma levels were measured by a solid-phase enzyme-linked immunosorbent assay. The frequency of the C allele and GC+CC genotype in MIF-173G/C was over-represented in spinal TB patients. The mean MIF mRNA level in spinal TB patients and patients with the GG and GC+CC genotype were significantly lower than controls; however, our study also indicated that the MIF concentration in spinal TB patients and patients with the GG and GC+CC genotypes were significantly higher than controls. Spinal TB patients with the GG genotype had higher MIF plasma levels than patients with the GC+CC genotype. The C-reactive protein level and erythrocyte sedimentation rate was correlated with the MIF plasma level. In summary, the association between the MIF-173G/C genetic polymorphism, reduced transcript and increased plasma levels of MIF in spinal TB patients, and MIF may play an important role in the occurrence, development, and damage of spinal TB in the northern Province population of China.

Evaluating macrophage migration inhibitory factor 1 expression as a prognostic biomarker in colon cancer.

Several studies indicate that macrophage migration inhibitory factor 1 plays a role for tumor progression in colon cancer. We investigated whether determination of migration inhibitory factor 1 mRNA expression levels in lymph nodes of colon cancer patients could be used as a prognostic marker. Expression levels of migration inhibitory factor 1 and carcinoembryonic antigen mRNAs were assessed in primary tumors and regional lymph nodes of 123 colon cancer patients (stages I-IV), and in colon cancer- and immune cell lines using quantitative reverse transcriptase-polymerase chain reaction. Expression of migration inhibitory factor 1 protein was investigated by two-color immunohistochemistry and immunomorphometry. Migration inhibitory factor 1 mRNA was expressed at 60 times higher levels in primary colon cancer tumors compared to normal colonic tissue (medians 8.2 and 0.2 mRNA copies/18S rRNA unit; p < .0001). A highly significant difference in mRNA expression levels was found between hematoxylin-eosin positive lymph nodes and hematoxylin-eosin negative lymph nodes (p < .0001). Migration inhibitory factor 1 and carcinoembryonic antigen proteins were simultaneously expressed in many colon cancer-tumor cells. Kaplan-Meier survival model and hazard ratio analysis, using a cutoff level at 2.19 mRNA copies/18S rRNA unit, revealed that patients with lymph nodes expressing high levels of migration inhibitory factor 1 mRNA had a 3.5-fold (p = .04) higher risk for recurrence, associated with a small, but significant, difference in mean survival time (7 months, p = .03) at 12 years of follow-up. Although migration inhibitory factor 1 mRNA expression levels were related to severity of disease and lymph node analysis revealed that colon cancer patients with high levels had a shorter survival time after surgery than those with low levels, the difference was small and probably not useful in clinical practice.

Key role of MIF-related neuroinflammation in neurodegeneration and cognitive impairment in Alzheimer\u2019s disease

BackgroundMacrophage Migration Inhibitory Factor (MIF) is a potent proinflammatory cytokine that promotes the production of other immune mediators. MIF is produced by most cell types in the brain including microglia, astrocytes and neurons. Enhanced expression of MIF might contribute to the persistent activation of glial, chronic neuroinflammation and neurodegeneration. Here, we investigated the effect of MIF on inflammatory markers and spatial learning in a mouse model of sporadic AD and on tau pathology in AD patients.MethodsWe examined the effects of MIF deficiency and pharmacological MIF inhibition in vitro and in vivo. In vitro, quantitative PCR and ELISA were used to assess cytokine production of STZ-treated glial cells. In vivo, C57BL/6 mice were subjected to intracerebroventricular streptozotocin injection (3 mg/kg, ICV-STZ). Neuroinflammation and contextual learning performance were assessed using quantitative PCR and fear conditioning, respectively. Pharmacological MIF inhibition was achieved with intraperitoneal injections of ISO-1 (daily, IP, 20 mg/kg in 5% DMSO in 0.9% NaCl) for 4 weeks following ICV-STZ injection. The findings from ISO-1 treated mice were confirmed in MIF knockout C57BL/6. To assess the role of MIF in human AD, cerebrospinal fluid levels of MIF and hyperphosphorylated tau were measured using ELISA.ResultsAdministration ICV-STZ resulted in hippocampal dependent cognitive impairment. MIF inhibition with ISO-1 significantly improved the STZ-induced impairment in contextual memory performance, indicating MIF-related inflammation as a major contributor to ICV-STZ-induced memory deficits. Furthermore, inhibition of the MIF resulted in reduced cytokine production in vitro and in vivo.In human subjects with AD at early clinical stages, cerebrospinal fluid levels of MIF were increased in comparison with age-matched controls, and correlated with biomarkers of tau hyper-phosphorylation and neuronal injury hinting at MIF levels as a potential biomarker for early-stage AD.ConclusionsThe present study indicates the key role of MIF in controlling the chronic cytokine release in neuroinflammation related to tau hyperphosphorylation, neurodegeneration, and clinical manifestations of AD, suggesting the potential of MIF inhibition as therapeutic strategy to slow down neurodegeneration and clinical disease progression.

Macrophage migration inhibitory factor modulates proliferation, cell cycle, and apoptotic activity in head and neck cancer cell lines

Background/purposeMacrophage migration inhibitory factor (MIF) is a multifunctional cytokine that contributes to the progression of several cancers. MIF overexpression has been reported in head and neck squamous cell carcinoma (HNSCC) patients. However, the exact role of MIF in HNSCC is not fully understood. Our aim was to evaluate the amount of secreted MIF and the role of MIF in the proliferation, cell cycle, and apoptosis in HNSCC cell lines.Materials and methodsGenetically matched HNSCC cell lines derived from primary (HN18 and HN30) and metastatic sites (HN17 and HN31) from the same patient were used in this study. The MIF levels in conditioned media from the HNSCC cell lines were evaluated using ELISA. The HNSCC cell lines were treated with recombinant MIF at concentrations 25, 50 and 100 ng/ml, and cell proliferation was evaluated by MTT assay. A proliferative dose of MIF was used to treat the cells then, cell cycle, and apoptotic status were determined by flow cytometry.ResultsThe HNSCC-secreted MIF concentration ranged from 49.33 to 973 pg/ml. Exogenous MIF (25 ng/ml) significantly increased HN18, HN30, and HN31 cell proliferation. Moreover, MIF induced cell cycle progression and inhibited apoptosis in these cells. However, MIF did not affect growth or apoptosis in HN17 cell.ConclusionMIF secreted from the HNSCC cell lines were evaluated. Exogenous MIF promotes various effects on proliferation, cell cycle, and apoptosis in HNSCC cells.

Diagnostic Values of Inflammatory and Angiogenic Factors for Acute Joint Bleeding in Patients With Severe Hemophilia A.

This study was conducted to assess the levels of inflammatory factors and angiogenic factors in patients with severe hemophilia A and evaluate their diagnostic values for acute joint bleeding. This study included a total of 144 patients with severe hemophilia A. Of them, 66 had acute joint bleeding. Ninety healthy volunteers were recruited as control. The levels of leukocytes, monocytes, platelets, hemoglobin, phagocyte migration inhibitory factor (MIF), plasminogen, fibrin/fibrinogen degradation products, d-dimer, and α2 antifibrinolytic enzyme were measured using hematology analyzer. Thrombomodulin, endostatin, intercellular adhesion molecule 1, and vascular endothelial growth factor (VEGF) were assessed using enzyme-linked immunosorbent assay. Logistic regression analysis was performed to analyze the factors affecting acute joint bleeding. Compared with healthy volunteers, the levels of leukocytes, C-reactive protein (CRP), MIF, and VEGF were significantly (P < .05) elevated in the patients with severe hemophilia A and were significantly higher in patients with joint bleeding than in patients with nonbleeding (P < .05). Multivariate analysis showed that CRP and VEGF were independent risk factors for acute joint bleeding (P < .05). The area under the curve, sensitivity, and specificity of CRP for the diagnosis of acute joint bleeding were 0.829, 88.43%, and 67.87%, respectively, and those of VEGF were 0.758, 82.8%, and 68.3%, respectively. The levels of inflammatory factors and angiogenesis factors are elevated in patients with severe hemophilia A and both CRP and VEGF are closely related to acute joint bleeding and may be used as potential biomarkers for predicting acute joint bleeding in patients with severe hemophilia A.

Serum migration inhibitory factor levels in periodontal health and disease, its correlation with clinical parameters.

Periodontal infections are an important risk factor for systemic disease and are driven primarily by the cytokines. Migration Inhibitory Factor (MIF) is a key cytokine which mediates acute and chronic inflammation alongside, a molecular link between chronic inflammation and immune mediated conditions. Hence, the present study was carried to measure the serum MIF levels in periodontal health, disease and to correlate the levels with the clinical parameters. Sixty subjects were divided into three groups (each group n = 20) based on the gingival index (GI), probing pocket depth (PPD), and clinical attachment level (CAL) as group I healthy; group II gingivitis; and group III chronic periodontitis. The serum MIF level was measured using quantitative sandwich enzyme immunoassay technique. Highest level was detected in Group III with a mean of 71.8 ng/ml and the lowest in group I (6.1 ng/ml). Serum MIF levels did not correlate with the clinical parameters. Increased serum MIF levels in chronic periodontitis patients suggest its role as an inflammatory biomarker and may have a role in inflating the systemic inflammation. Summary: Serum Migration inhibitory factor can be used as an inflammatory marker for periodontal disease.

Upregulation of MIF as a defense mechanism and a biomarker of Alzheimer\u2019s disease

BackgroundMacrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine. Chronic inflammation induced by amyloid β proteins (Aβ) is one prominent neuropathological feature in Alzheimer’s disease (AD) brain.MethodsElisa, Western blot, and immunohistochemical staining analysis were performed to examine the level of MIF protein in CSF and brain tissues. MTT and LDH assays were used to examine the neurotoxicity, and the Morris Water Maze test was performed to examine the cognitive function in the MIF+/−/APP23 transgenic mice.ResultsMIF expression was upregulated in the brain of AD patients and AD model mice. Elevated MIF concentration was detected in the cerebrospinal fluid of AD patients but not in that of the patients suffering from mild cognitive impairment and vascular dementia. Reduced MIF expression impaired learning and memory in the AD model mice. MIF expression largely associates with Aβ deposits and microglia. The binding assay revealed a direct association between MIF and Aβ oligomers. Neurons instead of glial cells were responsible for the secretion of MIF upon stimulation by Aβ oligomers. In addition, overexpression of MIF significantly protected neuronal cells from Aβ-induced cytotoxicity.ConclusionOur study suggests that neuronal secretion of MIF may serve as a defense mechanism to compensate for declined cognitive function in AD, and increased MIF level could be a potential AD biomarker.

Reduction in Plasma Macrophage Migration Inhibitory Factor and Angiopoietin-2 Levels during Venoarterial Extracorporeal Membrane Oxygenation Support

Purpose Both macrophage migration inhibitory factor (MIF) and angiopoietin-2 (Ang-2) have been linked to poor outcomes in cardiogenic shock (CS). These proteins are rapidly released from intracellular storage and have profound effects on the cardiopulmonary vasculature . We describe the changes in plasma MIF and Ang-2 in patients with CS supported with VA ECMO. Methods All patients supported with VA ECMO for CS in our center were enrolled. Blood samples were drawn at the following time points: within 24 hrs of ECMO (baseline), at 72 hours, and on the day of the weaning study (4-12d). MIF and Ang-2 were measured using commercially available ELISA (R&D Systems Inc., Minneapolis, MN). Results Twenty-three ECMO patients were studied. At baseline, both MIF and Ang-2 were significantly elevated compared to controls (n=9) (455±514 vs 1.5±0.7 ng/mL, p Conclusion CS is associated with significant derangement of plasma MIF and Ang-2 that improves with circulatory support . Importantly, patients who recovered had lower levels of MIF at presentation. Further study of these mediators may identify novel targets for therapy in cardiogenic shock.

Prognostic value of serum macrophage migration inhibitory factor levels in pulmonary tuberculosis

BackgroundMacrophage migration inhibitory factor (MIF) makes chemokine-like functions and plays critical roles in various inflammatory diseases. This study was designed to explore the significance of MIF serum levels in predicting the prognosis of pulmonary tuberculosis (PTB) following anti-TB treatment.MethodsPatients diagnosed with culture-confirmed PTB without treatment were included and the serum was collected. Levels of MIF in serum were quantified with immunoassay, and the levels of established biomarkers were also determined, including C-reactive protein (CRP) and Interleukin 6 (IL-6). The outcome was estimated with all-cause mortality, with the mortality in 12 months as the primary outcome and the mortality in 3, 6, 9 months as other outcomes. The prognostic value of MIF and other factors in PTB were tested.ResultsTwo hundred eighty-seven PTB patients were included. The median MIF levels in patients with advanced disease, disseminated and drug-resistant TB were significantly higher than that observed in mild -to- moderate disease, non-disseminated and drug-sensitive TB. MIF levels in patients with the outcome of death were higher than those survived [28.0 ng/ml (Inter-quartile range [IQR]: 24.2–33.1) vs. 22.3 ng/ml (IQR: 18.7–26.5); P < 0.001]. Multivariate model analysis was performed for comparing the highest quartiles to the lowest quartile of MIF levels. MIF levels were related to the mortality, with an elevated mortality risk of 236% [Odds ratio (OR) = 3.36; 95% Confidence interval (CI): 1.21–15.14; P = 0.012]. The model was re-analysis after combing MIF with currently established risk indicators. The obtained Area Under the Receiver Operating Characteristic Curve (±standard error) was elevated from 0.81 (±0.035) to 0.84 (±0.031), with a significant difference before and after adding the MIF (difference, 0.03[0.004]; P = 0.03).ConclusionSerum level of MIF was a better biomarker than CRP or IL-6 for predicting death in HIV-negative PTB patients, and increased MIF serum levels were related to higher mortality.

Use of the routine complete blood count to predict steroid resistance in patients with chronic obstructive pulmonary disease

The aimof the present study was to investigate the significance of complete blood count, lymphocyte subpopulations, and cytokines in the peripheral blood in order to evaluate steroid resistance in patients with chronic obstructive pulmonary disease (COPD).Methods.Forty five patients with acute exacerbation of COPD (AECOPD) who underwent bronchoscopy the next day after hospital admission were included in the study. The patients were considered as steroid-sensitive or steroid-resistant according to the ability of dexamethasone to inhibit 50% of interleukin-8 production by alveolar macrophages. Complete blood count, lymphocyte subpopulations, cytokines, immunoglobulin E, and hormone level were measured in the peripheral blood of all patients with COPD.Results.Macrophage migration inhibitory factor (MIF) level, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were higher, and absolute and relative eosinophil numbers were lower in steroid-resistant patients with COPD compared to steroid-sensitive COPD patients. Absolute eosinophil number below the cut-off value of 0.126 × 109/L was predictive for steroid resistance with the sensitivity of 83.3%, the specificity of 55.6% and the area under ROC curve (AUC) of 0.677. Relative eosinophil number below 1.2% predicted steroid resistance with sensitivity, specificity and AUC of 83.3%, 63.0%, and 0.751, respectively. NLR, PLR, and MIF higher than 2.75, 116, and 2.24 ng/mL, respectively, predicted steroid resistance with the sensitivities of 66.7%, 61.1%, and 72.2%, respectively; the specificities of 74.1%, 77.8%, and 70.4%, respectively; and the AUCs of 0.731, 0.678, and 0.740, respectively. The combination of relative eosinophil number, NLR and PLR increased the sensitivity to 83.3%, specificity to 77.8%, and AUC to 0.805. The combination of relative eosinophil number, PLR and MIF increased the sensitivity to 83.3%, specificity to 88.9%, and AUC to 0.889.Conclusion.Steroid-resistant and steroid-sensitive COPD patients differ in absolute and relative eosinophil numbers, LNR, PLR, and MIF level. These parameters could be used to predict steroid resistance in COPD.