Circulating Macrophage Migration Inhibitory Factor Levels Research Articles

High circulating MIF levels indicate the association with atypical antipsychotic-induced adverse metabolic effects.

Atypical antipsychotics (AAPs) are primary medications for schizophrenia (SZ). However, their use is frequently associated with the development of adverse metabolic effects, and the mechanisms behind these negative effects remain inadequately elucidated. To investigate the role of macrophage migration inhibitory factor (MIF) in regulating antipsychotic-induced metabolic abnormalities, between 2017 and 2020, a cross-sectional study was conducted, involving 142 healthy individuals and 388 SZ patients undergoing treatment with either typical antipsychotic (TAP) or AAP medications. Symptoms of SZ patients were evaluated using the Positive and Negative Syndrome Scale (PANSS), and measurements of metabolic indices and plasma MIF levels were performed on all individuals. A significant increase in plasma MIF levels was observed in groups receiving five major AAP monotherapies in comparison to healthy controls (all p < 0.0001). There was no such increase shown in the group receiving TAP treatment (p > 0.05). Elevated plasma MIF levels displayed a notable correlation with insulin resistance (β = 0.024, p = 0.020), as well as with the levels of triglycerides (β = 0.019, p = 0.001) and total cholesterol (β = 0.012, p = 0.038) in the groups receiving AAPs. However, while the TAP group also displayed certain metabolic dysfunction compared to healthy controls, no significant association was evident with plasma MIF levels (all p > 0.05). In conclusion, plasma MIF levels exhibit a distinctive correlation with metabolic abnormalities triggered by AAPs. Hence, there is potential for further development of MIF as a distinctive marker for monitoring adverse metabolic effects induced by AAPs in clinical settings.

Extracellular macrophage migration inhibitory factor (MIF) downregulates adipose hormone-sensitive lipase (HSL) and contributes to obesity

Attenuation of adipose hormone sensitive lipase (HSL) may impair lipolysis and exacerbate obesity. We investigate the role of cytokine, macrophage migration inhibitory factor (MIF) in regulating adipose HSL and adipocyte hypertrophy. Extracellular MIF downregulates HSL in an autocrine fashion, by activating the AMPK/JNK signaling pathway upon binding to its membrane receptor, CD74. WT mice fed high fat diet (HFD), as well as mice overexpressing MIF, both had high circulating MIF levels and showed suppression of HSL during the development of obesity. Blocking the extracellular action of MIF by a neutralizing MIF antibody significantly reduced obesity in HFD mice. Interestingly, intracellular MIF binds with COP9 signalosome subunit 5 (Csn5) and JNK, which leads to an opposing effect to inhibit JNK phosphorylation. With global MIF deletion, adipocyte JNK phosphorylation increased, resulting in decreased HSL expression, suggesting that the loss of MIF's intracellular inhibitory action on JNK was dominant in Mif−/− mice. Adipose tissue from Mif−/− mice also exhibited higher Akt and lower PKA phosphorylation following HFD feeding compared with WT, which may contribute to the downregulation of HSL activation during more severe obesity. Both intracellular and extracellular MIF have opposing effects to regulate HSL, but extracellular actions predominate to downregulate HSL and exacerbate the development of obesity during HFD.

1598-P: MIF-upregulated CD74 in Liver Contributes to the Development of NAFLD

Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic dysfunctions, such as obesity. Macrophage migration inhibitory factor (MIF), a pro-cytokine, was also identified to regulate NAFLD, but the molecular mechanisms remain unclear. We presently indicated that MIF has a non-inflammatory effect on triggering NAFLD through upregulating its cell membrane receptor, CD74. MIF increased CD74 protein rather than gene expression in liver cells in a time-dependent manner. That was not associated with any changes in the expression of pro-inflammatory factors, such as TNF-α, IL-6 and IL-1β. In a MIF overexpressed animal model (Mif lung Tg), high circulating MIF levels increased hepatic CD74 proteins but not genes in the absence of inflammation in the liver. High fat diet also increased circulating MIF levels leading to an upregulation of hepatic CD74. All these animal models with high circulating MIF and hepatic CD74 were accompanied with steatosis and fibrosis in the liver. These alterations could be reversed by either MIF neutralization or MIF knockout. Caspase 4 facilitates the degradation of CD74. MIF endocytosis inhibited caspase 4 cleavage and activation. Thus, inhibition of MIF upregulated cleaved caspase 4 leading to a degradation in CD74. Overall, our findings indicate that MIF stabilizes CD74 through suppressing caspase 4 and this may be an important mechanism in regulating NAFLD in the absence of inflammation. Disclosure L. Chen: None. L. Li: None. Y. Huang: None. X. Chen: None. Y. Qi: None. H. Tong: None. H. Wu: None. D. Qi: None. Funding Canadian Institutes of Health Research (PJT156116); Research and Development Corporation; National Sciences and Engineering Research Council of Canada (RGPIN-2017-04542); National Institutes of Health (AR-078334); China Scholarship Council (to L.C., Y.H., L.L.)

1615-P: The Peripheral and Central Cross Talk Mediated by Adipose MIF—A Novel Mechanism of Hyperphagia following Olanzapine Treatment

Olanzapine is one of the first-line antipsychotic medications but it usually induces metabolic side effects, characterized by obesity. We previously indicated that olanzapine leads to hyperphagia through the effects of a proinflammatory cytokine, macrophage migration inhibitory factor (MIF) in the hypothalamus. However, whether olanzapine's upregulated peripheral MIF could affect the central mechanism is currently unknown. Our present study found that olanzapine increases ectopic expression of dopamine receptor 1 (DRD1) in adipocytes which relatively upregulates MIF expression and release through a PKA/CREB signaling pathway. In global MIF knockout mice, MIF accumulation appears in the hypothalamus following peripheral injection of recombinant MIF proteins, suggesting that peripheral MIF indeed travels to the hypothalamus. Mif Lung Tg mice (MIF overexpression in the lung) with increased circulating MIF levels had hyperphagia and activation of the CaMKKβ/AMPK/AgRP signaling pathway in the hypothalamus. Overall, our study for the first time proved that adipose-derived MIF is a crucial factor in regulating metabolic side effects induced by olanzapine. Disclosure X.Chen: None. Y.Huang: None. Y.Qi: None. L.Chen: None. L.Li: None. P.Gao: None. D.Cui: None. D.Qi: None. Funding National Sciences and Engineering Research Council of Canada (RGPIN-2017-04542); Canadian Institutes of Health Research (PJT-156116); China Scholarship Council (202106230212)

Long-term prognostic value of macrophage migration inhibitory factor in ST-segment elevation myocardial infarction patients with metabolic syndrome after percutaneous coronary intervention.

Metabolic syndrome (MetS) is a major risk factor for cardiovascular disease and negatively affecting the prognosis of patients with ST elevation myocardial infarction (STEMI). Macrophage migration inhibitory factor (MIF) is a multipotent cytokine involved in various cardiovascular and inflammatory diseases. In this prospective study, we investigate the value of MIF in the long-term prognosis of STEMI combined with MetS after emergency PCI. Circulating MIF levels were measured at admission, and major adverse cardiovascular and cerebrovascular events (MACCE) were monitored during the follow-up period of 4.9 (3.9–5.8) years. MACCE occurred in 92 patients (22.9%), which was significantly higher in MetS (69/255, 27.1%) than in the non-MS subgroup (23/146, 15.8%, P < 0.05). Patients with MetS developed MACCE had the highest admission MIF level. Kaplan-Meier survival analysis using the cutoff value of admission MIF (143 ng/ml) showed that patients with a higher MIF level had a greater incidence of MACCE than those with lower MIF levels in both the MetS (P < 0.0001) and non-MetS groups (P = 0.016). After adjustment for clinical variables, the value of MIF ≥ 143 ng/ml still had the predictive power for the MetS group [HR 9.56, 95% CI (5.397–16.944),P < 0.001]; nevertheless, it was not the case in the non-MetS group. Our findings indicated that MetS is a critical risk factor for adverse clinical outcomes in patients with STEMI, and a high admission MIF level has predictive power for the long-term MACCE, which is superior in STEMI patients with MetS and better than other traditional predictors.

Circulating MIF Associated With Disease Severity and Clinical Response of Sublingual Immunotherapy in House Dust Mite-Induced Allergic Rhinitis.

Background: Macrophage migration inhibitory factor (MIF) is described as a pro-inflammatory cytokine involved in many inflammatory and allergic disorders, but the role of MIF in allergic rhinitis (AR) remains poorly clarified. The aim of this study was to investigate the association between circulating MIF levels and house dust mite (HDM)-induced AR, and evaluate MIF as a potential biomarker in reflecting disease severity and predicting the clinical response of sublingual immunotherapy (SLIT) in HDM-induced AR patients. Methods: In this study, we enrolled 160 persistent HDM-induced AR patients (AR group), including 48 mild AR patients (MAR group) and 112 moderate–severe AR patients (MSAR group), and 77 healthy controls (HC group). Circulating levels of MIF were measured by ELISA, and the relationship between MIF concentrations and disease severity was assessed. In the MSAR group, 106 patients were assigned to receive SLIT for 3 years. At the end of the study, patients were categorized into good response group and poor response group, and associations between clinical variables or biomarkers and clinical response were analyzed by the multivariate regression analysis. Results: The concentrations of serum MIF were significantly higher in AR patients than in HCs, especially in those with MSAR. Moreover, circulating MIF levels were positively correlated with TNSS, VAS, serum HDM–specific IgE, total IgE, blood eosinophil count, and blood eosinophil percentage (all p < 0.05). Eighty MSAR patients finally completed SLIT, 45 patients obtained good response, and 35 patients resulted in poor response. The serum levels of MIF were significantly lower in the good-response group than in the poor-response group (p < 0.001). The receiver operating characteristic analysis for MIF showed good accuracy for predicting clinical response of SLIT (area under the curve = 0.877, p < 0.001). The multivariate regression analysis demonstrated that serum MIF was an independent factor for SLIT responsiveness. Conclusion: Serum MIF appeared to be an important biological indicator in reflecting disease severity and an independent predictor for clinical responsiveness of SLIT in HDM-induced AR patients.

197-LB: The Regulation of HSL by Macrophage Migration Inhibitory Factor (MIF) Contributes to Adipocyte Hypertrophy and Development of Obesity

Inflammation is associated with lipolysis in adipose tissue. HSL is a key enzyme in mediating lipolysis through augmenting hydrolysis of triglycerides and diacylglycerides. Our study found that the procytokine MIF has both transcriptional and non-transcriptional effects on mediating HSL through activating AMPK signaling pathway. The activated AMPK downregulates HSL gene expression in adipocytes. It also upregulates a phosphorylation of HSL Ser565, an inhibitory phosphorylation site, leading to the reduction of HSL active site, Ser563 phosphorylation. These mechanisms are operative in either transgenic overexpressed MIF mouse models or WT mice with high circulating MIF levels following a high caloric diet feeding (HFD). The MIF/AMPK/HSL axis regulates the development of adipocyte hypertrophy and obesity. We also confirm that high plasma MIF levels are associated with decreased adipose HSL gene expression in human obesity. Interestingly, in Mif-/-mice, HSL gene expression is also inhibited, suggesting that MIF genotype is important to maintain adipose HSL expression. Following HFD feeding, Mif-/-mice demonstrates higher Akt and lower PKA phosphorylation, which further decrease HSL activation and exacerbate obesity compared to WT. Thus, HSL regulation by MIF may be an important molecular mechanism in the development of obesity.View largeDownload slideView largeDownload slide DisclosureL. Chen: None. Y. Huang: None. L. Li: None. H. Zabihi: None. Y. Qi: None. L. Leng: None. G. Sun: None. R. Bucala: None. D. Qi: None.FundingNational Sciences and Engineering Research Council of Canada (RGPIN-2017-04542); Canadian Institutes of Health Research (PJT-156116)

Single-nucleotide polymorphism and haplotype analysis of macrophage migration inhibitory factor gene and its correlation with serum macrophage migration inhibitory factor levels in North Indian psoriatic patients with moderate disease severity: A cross-sectional study.

Psoriasis is associated with significant morbidity and impaired quality of life. Identification of the host genes that influence disease susceptibility and can potentially guide future, targeted therapy is the need of the hour. The aim of the study was to investigate the associations of macrophage migration inhibitory factor (MIF) gene polymorphisms, that is, a 5-8-CATT tetra nucleotide repeats at -794 (-794*CATT5-8) and a single-nucleotide polymorphism at -173 (-173*G/C) with the risk of chronic plaque psoriasis and to observe the correlation, if any, of disease determinants with genetic functional variants and circulating MIF levels. Five hundred and seventeen individuals (265 psoriasis patients and 252 controls) were genotyped for MIF gene polymorphisms. Data were analyzed with respect to disease susceptibility, serum MIF levels, disease severity, age at onset, disease duration and presence of comorbidities. The presence of co-morbidities was more frequently noted in patients with late onset disease (P = 0.01). No statistically significant differences were observed either in genotype (P = 0.680) or allele frequency (P = 0.69) with respect to distribution of MIF-173*G/C polymorphism between patients and controls. The frequencies of genotypes -794*CATT 5/7 and 7/7 were significantly lower in patients (P = 0.027* and 0.038*, respectively). CATT*5/MIF-173*C haplotype occurred at a higher frequency in patients (odds ratio 3.03, 95% confidence intervals 1.09-8.47, P = 0.02). The mean serum MIF levels were significantly higher in patients as compared to controls (P < 0.001). The presence of either extended MIF -794*CATT repeats or C allele did not reveal any significant association with serum MIF levels or age at onset. Analysis of effect of various disease determinants revealed no significant association with genetic variants and serum MIF levels. The lesional expression of MIF could not be studied. Our results showed that CATT*5/MIF-173*C haplotype is associated with increased susceptibility to psoriasis vulgaris.

Association between MIF gene promoter rs755622 and susceptibility to coronary artery disease and inflammatory cytokines in the Chinese Han population

Macrophage migration inhibitory factor (MIF) is an essential mediator of atherosclerotic plaque progression and instability leading to intracoronary thrombosis, therefore contributing to coronary artery disease (CAD). In this study, we investigated the relationship between MIF gene polymorphism and CAD in Chinese Han population. Three single nucleotide polymorphisms (SNP, rs755622, rs1007888 and rs2096525) of MIF gene were genotyped by TaqMan genotyping assay in 1120 control participants and 1176 CAD patients. Coronary angiography was performed in all CAD patients and Gensini score was used to assess the severity of coronary artery lesions. The plasma levels of MIF and other inflammatory mediators were measured by ELISA. The CAD patients had a higher frequency of CC genotype and C allele of rs755622 compared with that in control subjects (CC genotype: 6.5% vs. 3.9%, P = 0.008, C allele: 24.0% vs. 20.6%, P = 0.005). The rs755622 CC genotype was associated with an increased risk of CAD (OR: 1.804, 95%CI: 1.221–2.664, P = 0.003). CAD patients with a variation of rs755622 CC genotype had significantly higher Gensini score compared with patients with GG or CG genotype (all P < 0.05). In addition, the circulating MIF level was highest in CAD patients carrying rs755622 CC genotype (40.7 ± 4.2 ng/mL) and then followed by GC (37.9 ± 3.4 ng/mL) or GG genotype (36.9 ± 3.7 ng/mL, all P < 0.01). Our study showed an essential relationship between the MIF gene rs755622 variation and CAD in Chinese Han population. Individuals who carrying MIF gene rs755622 CC genotype were more susceptible to CAD and had more severe coronary artery lesion. This variation also had a potential influence in circulating MIF levels.

Revisiting the secretion mechanism(s) of macrophage migration inhibitory factor-welcome to the "UPS club".

Revisiting the secretion mechanism(s) of macrophage migration inhibitory factor-welcome to the "UPS club".

Macrophage migration inhibitory factor promoter polymorphisms are associated with disease activity in rheumatoid arthritis patients from Southern Mexico.

BackgroundMacrophage migration inhibitory factor (MIF) is a cytokine capable of stimulating inflammatory cytokine and matrix metalloproteinase production from macrophages and synovial fibroblasts, which leads to persistent inflammation and bone degradation, two of the major pathological processes in rheumatoid arthritis (RA). The aim of this study was to evaluate the association of MIF promoter polymorphisms (−794CATT5‐8 rs5844572 and −173G > C, rs755622), circulating MIF levels, and mRNA expression with RA susceptibility and disease activity.MethodsA case–control study was conducted in 200 RA patients and 200 control subjects (CS) from Southern Mexico. Genotyping was performed by conventional PCR and PCR‐RFLP methods. MIF mRNA expression was quantified by real‐time PCR and MIF serum levels were determined by an ELISA kit.ResultsThe 7,7 (−794CATT5‐8) and −173CC (−173G > C) genotypes were associated with higher disease activity in RA patients. MIF serum levels were increased, and MIF mRNA expression was reduced in RA patients as compared to CS. In addition, RA patients with moderate disease activity had higher MIF levels than those with low disease activity. The −794CATT5‐8 and −173G > C MIF polymorphisms were not associated with RA susceptibility.ConclusionThese results suggest an important role of MIF polymorphisms and MIF serum levels with disease activity in RA.

Circulating MIF Levels Predict Clinical Outcomes in Patients With ST-Elevation Myocardial Infarction After Percutaneous Coronary Intervention

BackgroundThe purpose of the study was to assess the value of admission macrophage migration inhibitory factor (MIF) levels in predicting clinical outcomes in ST-elevation myocardial infarction (STEMI) patients. MethodsFor this study we recruited 498 STEMI patients after they received percutaneous coronary intervention (PCI), 40 with stable angina pectoris and 137 healthy participants. Plasma MIF levels were measured at admission and after PCI. The primary end points were in-hospital mortality and major adverse cardio-and/or cerebrovascular events (MACCE) during hospitalization and 3.2-year follow-up period. ResultsAdmission MIF levels were elevated in 88.4% of STEMI patients over the upper reference limit of healthy controls and it was 3- to 7-fold higher than that in stable angina pectoris and control groups (122 ± 61 vs 39 ± 19 vs 17 ± 8 ng/mL; P < 0.001). Admission MIF levels were significantly higher in patients who died after myocardial infarction vs survivors. For predicting in-hospital mortality using the optimal cutoff value (127.8 ng/mL) of MIF, the area under the receiver operating characteristic curve for MIF was 0.820, similar area under the receiver operating characteristic curve values for predicting short-term outcomes were observed for high-sensitivity troponin T, CK-MB, N-terminal probrain natriuretic peptide, and Global Registry of Acute Coronary Events (GRACE) score. Although peak high-sensitivity troponin T and N-terminal probrain natriuretic peptide also predicted MACCE during the follow-up period, only higher admission MIF levels predicted in-hospital mortality and MACCE during the 3.2-year follow-up. Multivariate regression analysis showed the independent predictive value of a higher admission MIF level (≥ 127.8 ng/mL) on in-hospital mortality (odds ratio, 9.1; 95% confidence interval, 1.7-47.2) and 3.2-year MACCE (hazard ratio, 2.8; 95% confidence interval, 1.5-5.6). ConclusionsA higher admission MIF level is an independent predictor for in-hospital mortality and long-term MACCE in STEMI patients who underwent PCI.

Low expression Macrophage Migration Inhibitory Factor (MIF) alleles and tuberculosis in HIV infected South Africans

Host immunity is crucial for controlling M. tuberculosis infection. Functional polymorphisms in the cytokine macrophage migration inhibitory factor (MIF) show global population stratification, with the highest prevalence of low expression MIF alleles found in sub-Saharan Africans, which is a population with the greatest confluence of both TB and HIV infection and disease. We investigated the association between MIF alleles and tuberculosis (TB) and HIV in South Africa. We acquired clinical information and determined the frequency of two MIF promoter variants: a functional −794 CATT5-8 microsatellite and an associated −173 G/C SNP in two HIV-positive cohorts of patients with active laboratory-confirmed TB and in controls without active TB who were all HIV positive. We found a greater frequency of low expression MIF promoter variants (-794 CATT5,6) among TB disease cases compared to controls (OR = 2.03, p = 0.023), supporting a contribution of genetic low MIF expression to the high prevalence of TB in South Africa. Among those with HIV, circulating MIF levels also were associated with lower CD4 cell counts irrespective of TB status (p = 0.016), suggesting an influence of HIV immunosuppression on MIF expression.

Circulating macrophage migration inhibitory factor (MIF) in patients with heart failure

BackgroundHeart failure (HF) is characterized by impaired systolic ejection capacity and/or diastolic filling of the heart, leading to a multisystem disorder. Remote organ failure, systemic inflammation or pulmonary hypertension (PH) are hallmarks of the pathophysiological changes in HF. The Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that is involved in a variety of cardiovascular and inflammatory diseases. Circulating MIF levels and their potential role as a disease marker in the different subgroups of HF have not been investigated yet. We here aimed to unravel a potential role of MIF in HF. Methods and resultsMIF plasma levels were assessed in 249 consecutive patients with HF. MIF was detectable in all investigated subjects and showed no difference with regard to the nature of HF (preserved or reduced ejection fraction). Spearman correlation revealed an association with inflammatory biomarkers (white blood cell count r = 0.18, p = 0.005; c-reactive protein r = 0.20, p = 0.003). MIF was associated with higher pulmonary artery systolic pressure (PASP) as assessed by echocardiography (r = 0.23, p < 0.001). Log-transformed PASP was also independently associated with MIF in a multivariable linear regression model (p = 0.02). Follow-up (FU) data after 180 days revealed that patients with increased MIF values (in ng/ml) were more likely to reach the endpoint all-cause mortality (HR 1.01, 95% CI 1.004–1.02, p = 0.005, per unit change). ConclusionMIF is detectable in the circulation of patients with HF and might be associated with clinical endpoints in HF, markers of inflammation and PH. These promising results should stimulate further research to elucidate the role of MIF in the multisystem disorder of HF.

Circulating macrophage migration inhibitory factor levels and its polymorphisms in systemic lupus erythematosus: A meta-analysis.

The present study aimed to systemically review the evidence regarding the relationship between circulating macrophage migration inhibitory factor (MIF) levels and systemic lupus erythematosus (SLE), as well as the associations between several polymorphisms in the MIF gene and SLE susceptibility. We performed a meta-analysis of serum/plasma levels of MIF in SLE patients and controls and evaluated evidence of associations between the MIF -173 C/G allele and -794CATT5-8 polymorphisms and the associated risk for SLE. Nine studies were included in this meta-analysis. Meta-analysis indicated that MIF levels were significantly higher in the SLE group than in the control group (SMD = 1.154, 95% CI = 0.369-1.938, P = 0.004). Stratification by ethnicity showed significantly higher MIF levels in the SLE group representing Asian populations (SMD = 1.911, 95% CI = 0.871-2.951, P &lt; 0.001). MIF levels were significantly higher in the SLE group than in the control group in the age-and/or sex matched population, but not in the unmatched population (SMD = 1.236, 95% CI = 0.579-1.893, P &lt; 0.001; SMD = 1.118, 95% CI = -0.027-2.263, P = 0.056). However, results of the meta-analysis showed no association between SLE and the MIF -173 C allele, the -794CATT7 allele, and the -794CATT7-MIF-173C haplotype with high heterogeneity. Our meta-analysis demonstrated significantly higher circulating MIF levels in patients with SLE, but no evidence of associations between MIF -173 C/G and -794CATT5-8 polymorphisms and SLE susceptibility.

Relationship Between Serum Macrophage Migration Inhibitory Factor Level and Insulin Resistance, High-Sensitivity C-Reactive Protein and Visceral Fat Mass in Prediabetes

BackgroundGrowing evidence suggest that macrophage migration inhibitory factor (MIF) plays a vital role in glucose metabolism. We aimed to ascertain whether MIF levels are altered in subjects with prediabetes and also to determine the relationship between MIF and metabolic parameters as well as visceral fat mass. Material and MethodsThis cross-sectional study included 40 subjects with prediabetes and 40 age-, body mass index (BMI)- and sex-matched subjects with normal glucose tolerance. Circulating MIF levels were measured using enzyme-linked immunosorbent assay. Metabolic parameters of recruited subjects were evaluated. Visceral fat mass was measured using bioelectrical impedance method. ResultsCirculating MIF levels were found to be elevated in subjects with prediabetes compared to controls (26.46 ± 16.98 versus 17.44 ± 11.80 ng/mL, P = 0.007). MIF positively correlated with BMI, visceral fat mass and indirect indices of homeostasis model assessment of insulin resistance. In linear regression model, an independent association was found between MIF levels and metabolic parameters, including BMI, visceral fat mass and homeostasis model assessment of insulin resistance. Multivariate logistic regression analyses revealed that the odds ratio for prediabetes was higher in subjects in the highest quartile of MIF compared to those in the lowest quartile, after adjusting for potential confounders. ConclusionsIncreased MIF levels are associated with the elevation of prediabetic risk.

Associations between circulating macrophage migration inhibitory factor (MIF) levels and rheumatoid arthritis, and between MIF gene polymorphisms and disease susceptibility: a meta-analysis

AimTo systematically review evidence regarding the relationship between circulating macrophage migration inhibitory factor (MIF) levels and rheumatoid arthritis (RA), and the association between MIF gene polymorphisms and RA susceptibility.DesignWe performed...

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.

MIF reflects tissue damage rather than inflammation in post-cardiac arrest syndrome in a real life cohort

IntroductionFollowing successful resuscitation from cardiac arrest (CA), neurological impairment and other types of organ dysfunction cause significant morbidity and mortality—a condition termed post-cardiac arrest syndrome. Whole-body ischemia/reperfusion with oxygen debt activates immunologic and coagulation pathways increasing the risk of multiple organ failure and infection. We here examined the role of the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF) in post-cardiac arrest syndrome. MethodsMIF plasma levels of n=16 patients with return of spontaneous circulation (ROSC) after CA were assessed with a previously validated method and compared to markers of systemic inflammation and cellular damage. ICU patients without former CA and healthy volunteers served as controls. ResultsMIF levels in patients after ROSC were higher compared to those in healthy volunteers and ICU patients without CA. Kaplan–Meyer analysis revealed a distinctly elevated mortality since day one that further increased towards an elevated 60-days-mortality in patients with high plasma MIF. ROC curve identified plasma MIF as a predictor for mortality in patients after CA. Correlation with inflammatory parameters revealed that high MIF levels did not mirror post CA inflammatory syndrome, but distinctive cellular damage after ROSC as there were strong correlations with markers of cellular damage like LDH and GOT/GPT. ConclusionHigh MIF levels were associated with elevated 60-days-mortality and high MIF predicted mortality after CA. We found a close relation between circulating MIF levels and cellular damage, but not with an inflammatory syndrome.

The Association of Higher Plasma Macrophage Migration Inhibitory Factor Levels with Lower Bone Mineral Density and Higher Bone Turnover Rate in Postmenopausal Women.

BackgroundDespite evidence from animal and clinical studies showing the detrimental effects of macrophage migration inhibitory factor (MIF) on bone metabolism, there are no clinical studies relating circulating MIF levels to osteoporosis-related phenotypes. This cross-sectional study investigated the association of plasma MIF with bone mineral density (BMD), bone turnover markers (BTMs), and prevalence of osteoporosis in postmenopausal Korean women.MethodsA total of 246 women not taking any medications or diagnosed with any diseases that could affect bone metabolism were enrolled. BMD values at the lumbar spine, femoral neck, and total femur, and blood levels of MIF and BTMs were measured in all subjects. Osteoporosis was defined by World Health Organization criteria.ResultsBefore and after adjustment for confounding variables, higher MIF levels were significantly associated with lower BMD values at all measured sites and higher levels of all BTMs. All BMD values and BTMs significantly changed in a dose-dependent fashion across increasing MIF quartile. When participants were divided into two groups according to osteoporosis status, postmenopausal women with osteoporosis demonstrated 24.2% higher plasma MIF levels than those without osteoporosis (P=0.041). The odds ratio per each standard deviation increment of MIF levels for prevalent osteoporosis was 1.32 (95% confidence interval, 1.01 to 1.73).ConclusionThis study provides the first epidemiological evidence that higher plasma MIF may be associated with higher risk of osteoporosis resulting from lower bone mass and higher bone turnover rate, and thus it could be a potential biomarker of poor bone health outcomes in postmenopausal women.