Macrophage Migration Inhibitory Factor In Patients Research Articles

ROLE OF MACROPHAGE MIGRATION INHIBITORY FACTOR, CLUSTER OF DIFFERENTIATION 19 AND INTERLEUKIN 23 IN INDIVIDUALS INFECTED WITH Salmonella typhi

Salmonella enterica serovar typhi (S.typhi) is one of the most important gram negative bacteria that cause enteric fever and stimulate the immune response in infected patients. This study aimed to compare the humoral and cellular immune responses in patients infected with S.typhi. For this, the concentration of three immunological markers viz., Macrophage migration inhibitory factor (MIF), Cluster of Differentiation 19 (CD19), and Interleukin 23 (IL-23) were measured by the Enzyme-Linked Immunosorbent Assay in the serum of 54 S.typhi infected patients, and 31 healthy individuals. The results demonstrated a significant increase (P =<0.05) in the serum concentration of MIF in patients infected with acute infection of S. typhi compared with healthy individuals but there were no significant differences in chronic infection. While there was a significant increase (P =<0.05) in serum concentration of CD19 and IL-23 in patients infected with acute and chronic infection of S.typhi as compared with healthy individuals. In conclusion, macrophage migration inhibitory factor plays a vital role in patients infected with acute infection of S. typhi and has no synergism with T-cell and B-cell in acute and chronic infection.

Elevated serum macrophage migration inhibitory factor levels correlate with benign paroxysmal positional vertigo and recurrence events.

Objective: We aimed to assess the possible relations between serum levels of macrophage migration inhibitory factor (MIF), a central cytokine of the innate immunity and inflammatory response, and benign paroxysmal positional vertigo (BPPV) risk and BPPV recurrence events.Methods: In the present study, 154 patients with BPPV, and 100 age-and sex-matched control subjects were enrolled in the study. All the patients and controls underwent a complete audio‐vestibular test battery including the Dix–Hallpike maneuver and supine roll test. In the BPPV group, measurements of MIF levels were repeated 1 month after the vertigo attack. The patients were also divided into the recurrence group and the nonrecurrence group in the 1-year follow-up.Results: The serum levels of MIF in patients with BPPV were higher than in those controls (13.9[interquartile range {IQR}, 8.9–18.4] ng/ml vs. 9.8[7.8–11.8]; P<0.001). As a continuous variable, MIF was associated with increased risk of BPPV (odds ratio [OR] 1.21, 95% confidence interval [CI]: 1.11–1.39; P=0.004) in multiple regression analyses. Recurrent attacks of BPPV were reported in 35 patients, and those patients had higher levels of MIF than those patients were not recurrence (18.0[IQR, 13.6–22.2] ng/ml vs. 12.6[9.3–16.8] ng/ml). In multivariate models comparing the second (Q2), third (Q3) and fourth(Q4) quartiles against the first (Q1) quartile of MIF, levels of MIF in Q4 were associated with recurrent BPPV, and the odds were increased by approximately 305% (OR = 4.05; 95%CI: 1.65–15.44; P=0.009).Conclusions: Elevated MIF is positively correlated with BPPV risk and BPPV recurrence events, requiring further efforts to clarify the exact mechanism.

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.

Reduction of MMP-9 and MIF Levels is Associated with the Beneficial Effects of Cilostazol in the Patients with Silent Brain Infarcts

Silent brain infarcts (SBIs) are cerebral infarcts seen on brain computed tomography (CT) or magnetic resonance imaging (MRI) in the absence of any clinical symptoms of stroke. In a previous study, cilostazol was shown to prevent the appearance or progression of SBIs. The present study aimed to evaluate the possible mechanisms of cilostazol in its beneficial effects on patients with SBIs by serially measuring inflammation- and angiogenesisassociated biomarkers such as matrix metalloproteinase-9 (MMP-9), macrophage migration inhibitory factor(MIF), visceral fat–derived adipokine (visfatin), C-X-C motif ligand 12 (CXCL12), and vascular endothelial growth factor (VEGF). We consecutively enrolled 26 patients with SBIs. SBIs were interpreted by two neuroradiologists and two neurologists. MMP-9, MIF, visfatin, CXCL12, and VEGF were measured in fasting blood samples from these 26 patients and 10 healthy volunteers at baseline and after taking cilostazol (200 mg/day) for one week and for 3 months. Serum MMP-9 was higher in patients with SBIs than in healthy controls at baseline (p<0.05), and levels of MMP-9 and MIF decreased after taking cilostazol for 3 months (p<0.01). MMP-9 levels were also lower at 1 week in the cilostazol group (p<0.05). Cilostazol had no significant effect on the other inflammatory biomarkers such as visfatin, CXCL12 and VEGF. Cilostazol decreases the inflammatory biomarkers MMP-9 and MIF in patients with SBIs and it may contribute to its beneficial effects in these patients.

Monocyte chemoattractant protein 1 and macrophage migration inhibitory factor in children with type 1 diabetes.

Serum monocyte chemoattractant protein 1 (MCP-1) and macrophage migration inhibitory factor (MIF) could be involved in the pathophysiological process of diabetes. The aim of the study was to evaluate MCP-1 and MIF in patients with diabetes mellitus type 1 (T1DM) and to assess its relation to diabetic control. The study included 39 patients with type 1 diabetes and 38 healthy volunteers. Blood sample was taken for assessment of glycosylated hemoglobin, serum MIF and MCP-1. Serum MIF and MCP-1 were significantly higher in diabetic cases than in healthy controls. HbA1c levels, were significantly higher in cases than in controls. Serum MIF had a significant positive correlation with serum MCP-1 (r=0.361, p=0.03). No other significant correlation with glycosylated hemoglobin or duration of diabetes was detected. A significant increase of serum level of MIF and serum MCP-1 was found in patients with T1DM. These results support that MCP-1 and MIF could be a therapeutic target to treat diabetes and to prevent its complications.

Elevated serum levels of macrophage migration inhibitory factor and stem cell growth factor β in patients with idiopathic and systemic sclerosis associated pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) can be idiopathic or secondary to autoimmune diseases, and it represents one of the most threatening complications of systemic sclerosis (SSc). Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine with proinflammatory functions that appears to be involved in the pathogenesis of hypoxia-induced PH. In SSc patients, high serum levels of MIF have been associated with the development of ulcers and PAH. Stem cell growth factor β (SCGF β) is a human growth factor that, together with MIF, is involved in the pathogenesis of chronic spinal cord injury. The aim of our study was to measure serum levels of MIF in patients with idiopathic and SSc-associated PAH. We enrolled 13 patients with idiopathic PAH and 15 with SSc-associated PAH. We also selected 14 SSc patients without PAH and 12 normal healthy controls, matched for sex and age. PAH was confirmed by right hearth catheterism (mPAP>25 mmHg). MIF and SCGF β levels were measured by ELISA. We found significantly higher circulating levels of MIF and of SCGF β in patients with idiopathic PAH (P=0.03 and P=0.004) and with PAH secondary to SSc (P=0.018 and P=0.023) compared to SSc patients without PAH. Higher levels of MIF were found in those patients with an higher New York Heart Association (NYHA) class (P=0.03). We can hypothesize that MIF and SCGF β are able to play a role in PAH, both idiopathic or secondary, and in the future they may be evaluated as useful biomarkers and prognostic factors for this serious vascular disease.

A case-control study on the association of MIF -794 CATT5-8 and -173 G&gt;C polymorphisms and its serum levels and the clinical severity of multiple sclerosis in Mexican patients

Event Abstract Back to Event A case-control study on the association of MIF -794 CATT5-8 and -173 G>C polymorphisms and its serum levels and the clinical severity of multiple sclerosis in Mexican patients Victor A. Castaneda Moreno1, José F. Muñoz-Valle1*, Norma Torres Carrillo1, Oscar P. Gonzalez Perez1, 2, Miguel A. Macias Islas3, Jose L. Ruiz Sandoval4, Ofelia Padilla De La Torre3, Xochitl A. Trujillo Trujillo5 and Miguel Huerta Vieyra5 1 Universidad De Guadalajara, Mexico 2 Universidad de Colima, Mexico 3 Centro medico nacional de occidente, Neurologia Clinica, Mexico 4 Hospital Civil Fray Antonio Alcalde, Mexico 5 Universidad de Colima, Mexico The macrophage migration inhibitory factor (MIF), is one of the main cytokines involved in the tissular damage progression in several autoimmune diseases. This central role of MIF in inflammation and disease progression, suggest it might be a potential therapeutic target for multiple sclerosis (MS), however it is first necessary to know if it actually plays an important role on MS. We investigated whether the commonly occurring functional polymorphisms in the promoter of MIF have a significant impact on adults with MS in a Mexican Mestizo population. The patients for this study were recruited from the Centro Medico Nacional de Occidente, IMSS, in Guadalajara, Jalisco, Mexico, and the healthy subjects (HS) were recruited from the general population by invitation. A total of 200 patients and 200 HS were recruited from August 2013 to October 2014. Genotyping of -794 CATT5-8 (rs5844572) and -173 G>C (rs755622) polymorphisms was done through PCR and PCR-RFLP, respectively. MIF serum levels were determined by ELISA with a commercial kit provided by BioLegend. Statistical analysis was done with IBM’s SPSS v 20.0. Respect to the analysis of the serum levels of MIF there was significantly higher levels of MIF in MS patients (6.5 ng/ml) compared with HS (3.7 ng/ml) (p<0.01). We found a tendency to lower serum levels of MIF in patients that were on relapse (4.7 ng/ml) vs patients that were on remission (6.5 ng/ml), although this didn’t reach statistical significance (p=0.076). We also found a positive correlation (rs=0.267) between the serum levels of MIF on remission and the expanded disability status scale (EDSS) (p=0.009). On the analysis of the MIF polymorphisms genotypes and the clinical characteristics of MS patients, we found a significant association of the -173 GC genotype with a higher EDSS (p=0.027), as well as with a higher multiple sclerosis severity score (MSSS) (p=0.028). We also found an association of the -794 CATT 5/7 genotype with a higher MSSS (p<0.05). Finally, we found a significant association of the -794 CATT 5 allele with higher levels of MIF in serum of MS patients (carriers 7.59 ng/ml vs non carriers 5.35 ng/ml, p=0.026). In conclusion, elevated levels of MIF are associated with MS and seem to play a role in the disease progression as it rises in serum as increases EDSS. Also, the -794 CATT 5 allele is associated with higher MIF serum levels in MS, and the -794 CATT 5/7 genotype is associated with higher MSSS. Likewise, the -173 GC genotype is associated with higher EDSS and MSSS. However, further studies of other cytokines and their relationship with MIF are necessary to have a complete understanding of the role of this protein in MS. The present study was financed by the Consejo Nacional para la Ciencia y la Tecnología from Mexico, proyect number: 180663.

Chemokines mRNA expression in relation to the Macrophage Migration Inhibitory Factor (MIF) mRNA and Vascular Endothelial Growth Factor (VEGF) mRNA expression in the microenvironment of endometrial cancer tissue and normal endometrium: A pilot study

Tumor microenvironment inflammatory cells play a major role in cancer progression. Among these, the Tumor Associated Macrophages (TAMs) infiltration depends on the kind of chemokine, cytokines and growth factors secreted by the tumor cells and by the stroma in response to the cancer invasion.TAMs have been found to promote anti-tumor response in early stages and to stimulate neovascularization and metastases in advanced disease. In the microenvironment chemo-attractants of many human cancers, MIF and VEGF correlate with an increased TAMs recruitment. In addition, MIF enhances tumor cells metastases by modulating the immune responses and by promoting the angiogenesis related to VEGF. On the contrary the inhibition of MIF can lead to cell cycle arrest and apoptosis. Some chemokines (e.g. CXCL12, CXCL11, CXCL8) and their receptors, thanks to their ability to modulate migration and proliferation, are involved in the angiogenetic process.In this study we compared the expression of MIF mRNA with VEGF mRNA expression and with mRNA expression of other chemokines related to neo-angiogenesis, such as CXCL12, CXCL11, CXCL8 and CXCR4, in human endometrial cancer tissue (EC) and normal endometrium (NE).Fresh samples of EC tissue and NE were extracted from 15 patients with FIGO stage I–III undergoing primary surgery. Some of the tissue was sent for histology and part of it was treated with RNA later and stored at −80°C.Four patients dropped out. A significant up-regulation of MIF mRNA in EC tissue versus NE samples (P=0.01) was observed in all 11 patients. The MIF mRNA over-expression was coincident with a VEGF mRNA overexpression in 54% of patients (P=NS). MIF mRNA was inversely related to CXCL12 mRNA expression (P=0.01).MIF over-expression was significantly related to low grading G1–2 (P=0.01), endometrial type I (P=0.05), no lymphovascular spaces invasion (P=0.01) and 3years DFS (P=0.01).As reported in previous studies on patients with breast cancer, our data suggest that the up-regulation of MIF in patients with endometrial cancer might be related to the inhibition of distant and lymphatic spread.

Tear levels of macrophage migration inhibitory factor in vernal keratoconjunctivitis

Objective: The pathogenesis of vernal keratoconjunctivi­tis (VKC) is not fully understood and cannot be explained only with type I hypersensitivity reaction. The aim of this study was to determine the Macrophage migration inhibi­tory factor (MIF) levels in tear fluids of patients with VKC. Methods: Tear fluid samples were collected with micro­capillary tubes for hematocrit at the lateral canthus of patients in the supine position without any anesthesia. Tear levels of MIF were measured by ELISA kit. Tear fluid samples were collected from 10 healthy subjects and 20 patients with VKC. Results: Tear levels of MIF in patients with VKC were significantly higher than those in controls (p<0,001). Conclusion: These results suggested that MIF may have significant effect on the pathogenetic process of VKC.

A genetic role for macrophage migration inhibitory factor (MIF) in adult-onset Still's disease

IntroductionAdult-onset still's disease (AOSD) is a rare systemic inflammatory disorder in which abnormalities in inflammatory cytokines production appear to play a pathophysiological role. Our previous work has reported increased expression of macrophage migration inhibitory factor (MIF) and revealed its correlation with disease severity and activity in AOSD. A -173 G/C single nucleotide polymorphism (SNP) (rs755622) and a -794 CATT5-8 repeat (rs5844572) in the MIF promoter have been reported. In this study, we sought to explore the relationship between functional MIF promoter polymorphisms and MIF expression in AOSD.Methods100 patients and 200 controls were recruited in the study. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay was utilized to analyze the -173 G/C SNP (rs755622) and PCR-based size discrimination assay was applied to detect the -794 CATT5-8 repeat (rs5844572) in the MIF promoter. Plasma MIF levels were measured by ELISA. MIF mRNA levels were quantified by real-time reverse transcription (RT)-PCR. Bisulfate genomic sequencing was employed to evaluate DNA methylation status within the MIF promoter.ResultsWe identified that the frequencies of MIF -794 CATT5 (P = 0.001) allele and the expression of MIF (P <0.001) were increased in patients compared to healthy controls. Plasma levels of MIF in patients with CC genotype were higher than those of patients with GC or GG genotypes (P = 0.05). In patients with established AOSD, a higher frequency of -794 CATT7 containing MIF genotypes was observed in those with liver dysfunction (P = 0.009). Haplotype analysis revealed a higher representation of the MIF haplotype defined by -173*C/-794 CATT5 (C5) in AOSD patients (P = 0.001).ConclusionFunctional promoter polymorphisms in the MIF gene influence plasma MIF levels in AOSD and may contribute to disease susceptibility or clinical presentation of AOSD.

Increased Levels of Macrophage Migration Inhibitory Factor in Patients with Familial Mediterranean Fever

Objective: To determine the level of macrophage migration inhibitory factor (MIF), its relationship with Mediterranean fever (MEFV) gene mutations and oxidative stress in familial Mediterranean fever (FMF).Methods: Fifty one unrelated attack free FMF patients (24 M and 27 F, 32.8±8.7 years) and 30 healthy controls (16 M and 14 F, 32.7±7 years) were included in the study. Serum MIF, total oxidant status (TOS) and total anti-oxidant status (TAS) were studied.Results: Age, sex distribution, anthropometrical indices, smoking status, serum lipids and TAS concentrations were similar between the patients and controls. However; erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), MIF, and TOS were significantly higher in the patients' group compared with healthy subjects. MIF, TOS and TAS levels were not different between patients with or without M694V mutations.Conclusion: We found increased concentrations of MIF in patients with FMF. Increased MIF levels were significantly correlated with oxidative stress and in regression analysis MIF concentrations were independent from the inflammatory activity as assessed by ESR and CRP. M694V mutations seem no effect on MIF and oxidative stress.

Study on expression and change of peripheral blood macrophsge migration inhibitory factor in patients with acute cerebral infarction

[Objective]To explore the function of peripheral blood macrophage migration inhibitory factor (MIF) during cerebral infarction by studying the expression and change of MIF in patients with cerebral infarction.[Methods]The levels of plasma MIF were measured by enzyme linked immunosorbent assay (ELISA) and the levels of peripheral blood mononuclear cells '(PBMC) MIF mRNA were measured by real-time polymerase chain reaction (RT-PCR) in 68 patients at acute stage (1～3 days),subacute stage (10～14 days).Mean time,99 healthy persons mating cerebral infarction group in both sex and ages were measured.[Results]At acute stage,the levels of plasma M1F[(52.77 ± 25.42)ng/ml]and PBMC MIF mRNA (0.42 ± 0.37)in the patients with cerebral infarction were obviously higher than those of subacute stage[(39.20 ± 17.46)ng/ml,0.27 ± 0.29]and the healthy controls[(32.66 ± 27.92)ng/ml,0.24 ± 0.23](P ＜ 0.05).The levels of plasma MIF and PBMC MIF mRNA in the patients with cerebral infarction at subacute stage had no significant difference with those of the healthy controls (P＞ 0.05).[ConcIusions] The plasma level of MIF and the PBMC expression of MIF mRNA are in increased gradually,and then gradually drop down to normal level.Dynamic detections of the plasma level of MIF and the PBMC expression of MIF mRNA are useful for forecasting the development and prognosis of acute cerebral infarction. Key words: Cerebral infarction; Peripheral blood mononuclear cells; Macrophage migration inhibitory factor; Real-time polymerase chain reaction

Macrophage Migration Inhibitory Factor Is Enhanced in Acute Coronary Syndromes and Is Associated with the Inflammatory Response

BackgroundChronic inflammation promotes atherosclerosis in cardiovascular disease and is a major prognostic factor for patients undergoing percutaneous coronary intervention (PCI). Macrophage migration inhibitory factor (MIF) is involved in the progress of atherosclerosis and plaque destabilization and plays a pivotal role in the development of acute coronary syndromes (ACS). Little is known to date about the clinical impact of MIF in patients with symptomatic coronary artery disease (CAD).Methods and ResultsIn a pilot study, 286 patients with symptomatic CAD (n = 119 ACS, n = 167 stable CAD) undergoing PCI were consecutively evaluated. 25 healthy volunteers served as control. Expression of MIF was consecutively measured in patients at the time of PCI. Baseline levels of interleukin 6 (IL-6), “regulated upon activation, normal T-cell expressed, and secreted” (RANTES) and monocyte chemoattractant protein-1 (MCP-1) were measured by Bio-Plex Cytokine assay. C-reactive protein (CRP) was determined by Immunoassay. Patients with ACS showed higher plasma levels of MIF compared to patients with stable CAD and control subjects (median 2.85 ng/mL, interquartile range (IQR) 3.52 versus median 1.22 ng/mL, IQR 2.99, versus median 0.1, IQR 0.09, p<0.001). Increased MIF levels were associated with CRP and IL-6 levels and correlated with troponin I (TnI) release (spearman rank coefficient: 0.31, p<0.001). Patients with ACS due to plaque rupture showed significantly higher plasma levels of MIF than patients with flow limiting stenotic lesions (p = 0.002).ConclusionTo our knowledge this is the first study, demonstrating enhanced expression of MIF in ACS. It is associated with established inflammatory markers, correlates with the extent of cardiac necrosis marker release after PCI and is significantly increased in ACS patients with “culprit” lesions. Further attempts should be undertaken to characterize the role of MIF for risk assessment in the setting of ACS.

Macrophage Migration Inhibitory Factor Mediates Hypoxia-Induced Pulmonary Hypertension

Pulmonary hypertension (PH) is a devastating disease leading to progressive hypoxemia, right ventricular failure, and death. Hypoxia can play a pivotal role in PH etiology, inducing pulmonary vessel constriction and remodeling. These events lead to increased pulmonary vessel wall thickness, elevated vascular resistance and right ventricular hypertrophy. The current study examined the association of the inflammatory cytokine macrophage migration inhibitory factor (MIF) with chronic lung disease and its role in the development of hypoxia-induced PH. We found that plasma MIF in patients with primary PH or PH secondary to interstitial lung disease (ILD) was significantly higher than in the control group (P = 0.004 and 0.007, respectively). MIF involvement with hypoxia-induced fibroblast proliferation was examined in both a human cell-line and primary mouse cells from wild-type (mif⁺/⁺) and MIF-knockout (mif⁻/⁻) mice. In vitro, hypoxia-increased MIF mRNA, extracellular MIF protein accumulation and cell proliferation. Inhibition of MIF inflammatory activity reduced hypoxia-induced cell proliferation. However, hypoxia only increased proliferation of mif⁻/⁻ cells when they were supplemented with media from mif⁺/⁺ cells. This growth increase was suppressed by MIF inhibition. In vivo, chronic exposure of mice to a normobaric atmosphere of 10% oxygen increased lung tissue expression of mRNA encoding MIF and accumulation of MIF in plasma. Inhibition of the MIF inflammatory active site, during hypoxic exposure, significantly reduced pulmonary vascular remodeling, cardiac hypertrophy and right ventricular systolic pressure. The data suggest that MIF plays a critical role in hypoxia-induced PH, and its inhibition may be beneficial in preventing the development and progression of the disease.

Elevated Levels of Macrophage Migration Inhibitory Factor in Women with Metabolic Syndrome

Metabolic syndrome is a complex clinical disorder characterized by obesity, a disturbance of glucose metabolism, dyslipidemia, and hypertension, leading to increased cardiovascular risk. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine produced both by innate immune cells and by adipocytes, and it plays an important role in inflammatory and cardiovascular diseases. The goal of this study was to evaluate the expression of circulating MIF in patients with metabolic syndrome. A study was conducted involving 172 persons who attended the Jeju National University Hospital Health Promotion Center. Among the 172 subjects, 88 patients with metabolic syndrome and 84 healthy control subjects were included. Serum MIF levels were considerably higher in patients with metabolic syndrome than in healthy subjects (mean±SEM, 1413.0-pg/ml±102.6 vs. 1077.0-pg/ml±-91.3, p=0.016). Among the metabolic syndrome patients, MIF levels were significantly increased in women (1403.0-pg/ml±114.2 vs. 921.3 pg/ml±117.3, p=0.005), but not in men. Even after further linear regression adjustment for age and body mass index, the expression of MIF for women with metabolic syndrome was still clearly elevated when compared to healthy subjects (p=0.011). Circulating MIF concentrations showed a gender disparity between healthy and metabolic syndrome subjects. An elevation of systemic MIF in women with metabolic syndrome may contribute to pathogenesis of metabolic syndrome or to the development of metabolic syndrome-related diseases, such as atherosclerosis and type 2 diabetes mellitus.

Macrophage migration inhibitory factor in patients with vitiligo and relationship between duration and clinical type of disease

Vitiligo is a disorder of pigmentation characterized by the presence of depigmented skin macules. Cellular immunity is known to have a role in the pathogenesis of vitiligo. Macrophage migration inhibitory factor (MIF) is a potent activator of macrophages and is considered to play an important role in cell-mediated immunity. To determine serum level of MIF in patients with vitiligo and compare with healthy controls. We also aimed to determine whether there is a relationship between MIF levels and the disease duration, clinical vitiligo and involved body surface area (BSA) in patients with vitiligo. The study group comprised 30 patients with vitiligo (14 men, 16 women) and 30 healthy controls, matched for age and gender. Blood samples were taken for MIF analysis. The mean serum level of MIF in patients with vitiligo (40.83 +/- 31.66 pg/mL) was significantly higher than that of the control group (21.00 +/- 6.48 pg/mL) (P = 0.002). There was a positive correlation between disease duration and MIF levels (r = 0.601, P < 0.001). Mean MIF level of patients with acral and acrofacial vitiligo (n = 6) was 48.25 +/- 32.02 pg/mL, and of patients generalized vitiligo (n = 18) was 44.46 +/- 35.25 pg/mL. There was no significant difference between these two groups (P > 0.05). However there was a significant difference in MIF levels between patients with localized (20.41 +/- 5.23, n = 5) and acral-acrofacial (P = 0.02) vitiligo and those with generalized (P = 0.006) vitiligo. There was no relationship between BSA and MIF levels. Mean serum MIF level of patients with vitiligo was higher than that of controls, indicating that MIF has a role in the pathogenesis of vitiligo.

Development of a novel method to measure macrophage migration inhibitory factor (MIF) in sera of patients with rheumatoid arthritis by combined electrochemical immunosensor

Macrophage migration inhibitory factor (MIF) has a multitude of biological activity and is associated with a number of inflammatory and immune diseases, including rheumatoid arthritis (RA). The increased serum levels of MIF in patients not only suggest this protein as a marker for disease progression, but also as a potential therapeutic target. The aim of this study is to develop a novel electrochemical method to more precisely and conveniently measure MIF in patient sera. An IgM murine monoclonal antibody (mAb) against human MIF was prepared and used in the electrochemical immunosensor, with modified gold electrode coated with compounds of gold nanoparticles, titanium dioxide nanoparticles and thionine (NGP-NTiP-Thi) followed by adsorption of anti-MIF antibodies with IgM or IgG1 isotype. The IgM immunosensor recognized MIF in a linear relationship in the range of 0.03 and 230 ng/mL with the lower limit ( S/ N = 3) of 0.02 ng/mL. The measurement showed considerable levels of sensitivity, selectivity, stability and long-term maintenance of bioactivity, as shown by testing with serum MIF in RA patients as compared to healthy donors. The performance of the IgM immunosensor was also superior to IgG1 sensor. Thus, we have developed a novel measurement approach for serum MIF, which may have great potential in the clinic for monitoring the course of diseases associated with increased MIF.

Exhaustion is Associated With Low Macrophage Migration Inhibitory Factor Expression in Patients With Coronary Artery Disease

Macrophage migration inhibitory factor (MIF), a protein secreted by immune cells and the pituitary gland, may be associated with coronary artery disease (CAD) and the mental state of coronary patients. The first origin of MIF suggests positive, the second negative associations. The aim of this study was to explore the direction of the association of MIF with CAD and of MIF with exhaustion, if any. Participants were 194 patients who had been recently treated by percutaneous coronary intervention (PCI) and who were exhausted at the start of the study. Half entered a behavioral intervention program. MIF, C-reactive protein, interleukin (IL)-6, IL-1 receptor antagonist, and neopterin were measured in blood collected 6 weeks after PCI (baseline) and 6 and 18 months after baseline. A single measurement of MIF was also available for 129 age- and sex-matched healthy individuals (reference group). At baseline, MIF in patients undergoing PCI was significantly lower than in the reference group (p < .01). New cardiac events occurred twice as often in the lowest quartile than in the highest quartile of MIF concentrations. However, the association was not significant (chi(2) = 2.27; df = 3; p = .52). During follow up, MIF concentrations increased significantly in patients undergoing PCI (p < .001). At 18 months, MIF concentrations were significantly lower in the exhausted patients than in the nonexhausted patients (p = .02). hsCRP, IL-1ra, IL-6, and neopter in concentrations did not change over this time period. The data are suggestive of a negative association of MIF with CAD and of MIF with exhaustion. The observation that those patients who remained exhausted had lower concentrations of MIF fits into earlier observations that suggested that exhausted coronary patients may be characterized by a hypoactivity of the hypothalamic-pituitary-adrenocortical axis.

Correlation of rheumatoid arthritis severity with the genetic functional variants and circulating levels of macrophage migration inhibitory factor

To study whether genetic variants of macrophage migration inhibitory factor (MIF), the MIF -173G>C and CATT(5-8) alleles, are associated with disease severity and levels of circulating MIF in patients with rheumatoid arthritis (RA). Genotyping was performed in patients with early RA and in healthy controls. Demographic data, disease activity, and outcome measurements were compared between patients with and without the MIF variants. MIF -173G>C and CATT(5-8) polymorphisms were genotyped, and a newly developed enzyme-linked immunosorbent assay for human MIF was used. Allele and genotype distributions of the MIF -173G>C and CATT(5-8) polymorphisms were compared between patients and controls by chi-square test. Multiple regression analysis was performed to assess the independence of the MIF functional genetic variants as risk factors for radiologic joint damage. Genotyping of the -173G>C and CATT(5-8) polymorphisms of MIF in RA patients and healthy individuals (n = 277 each) revealed similar frequencies of genotypes and haplotypes in both groups. No significant differences in demographic or clinical features were observed between RA patients carrying the MIF -173C allele or the MIF CATT7 allele or both and non-carrier RA patients. Radiologic joint damage was significantly higher in patients carrying risk alleles of the MIF -173G>C or the MIF CATT(5-8) functional variants. No synergistic effects between both genetic variants were observed. Multivariate regression analysis revealed that presence of the MIF -173C/C and MIF CATT(7/7) genotypes and having 1 MIF -173C allele were independent prognostic variables. Carriership of the MIF -173C allele (P = 0.002) or MIF CATT7 allele (P = 0.004) was associated with significantly higher circulating MIF levels compared with those in subjects having none of the risk-conferring alleles, and greater circulating MIF levels correlated with more severe radiologic joint damage (r = 0.64, P = 0.001). The MIF polymorphisms are not associated with RA susceptibility but are associated with high levels of radiologic joint damage. High circulating MIF levels were shown to correlate strongly with radiologic joint damage, suggesting that MIF expression is genetically determined and can be used as a novel prognostic tool in RA.

Role of Macrophage Migration Inhibitory Factor in Conjunctival Pathology in Ocular Cicatricial Pemphigoid

Macrophage migration inhibitory factor (MIF) is a pleiotropic, proinflammatory cytokine that mediates various immunoinflammatory processes. Ocular cicatricial pemphigoid (OCP) is an autoimmune disease in which affected conjunctivae show features of an immunoinflammatory disease. In this study, the role of MIF in the pathogenesis of OCP was examined. The expression of MIF in conjunctival tissues of patients with OCP (n = 10) and normal subjects (n = 5) was studied by quantitative real-time PCR and immunohistochemistry. The production of MIF by conjunctival fibroblasts of normal control subjects and patients with OCP was determined, by using quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA). In addition, the effects of interleukin (IL)-1, tumor necrosis factor (TNF)-alpha, and transforming growth factor (TGF)-beta1 on the induction of MIF by conjunctival fibroblasts were studied by quantitative real-time PCR. To determine the relationship between conjunctival expression of MIF and accumulation of macrophages, in patients with OCP, a correlation study was performed. An increased conjunctival expression of MIF was detected in patients with OCP, both at the mRNA (by real-time PCR) and protein level (by immunohistochemistry), compared with normal control patients. The expression of MIF was detected in the epithelial cells and occasionally in the stromal cells in control conjunctival tissues, by immunohistochemistry. In contrast, a statistically significant increase (P < 0.0001) in the expression of MIF was detected in the stromal cells of conjunctival tissues obtained from patients with OCP (control: 4.89 +/- 0.5; OCP: 19.82 +/- 1.34). By quantitative real-time PCR, compared with control conjunctiva, an increase in the expression of MIF was detected in the conjunctiva obtained from patients with OCP. A similar increase in the expression of MIF was also detected in conjunctival fibroblasts of patients with OCP, compared with control fibroblasts, by quantitative real-time PCR. A significantly increased (P < 0.001) level of MIF was also detected in supernatant collected from conjunctival fibroblasts of patients with OCP (186 +/- 5.4), compared with supernatant collected from control fibroblasts (9.3 +/- 7.6). Moreover, IL-1, TNF-alpha, and TGF-beta1, known factors involved in the pathogenesis of OCP, were found to induce the expression of MIF by conjunctival fibroblasts. A statistically significant correlation (P < 0.0001, r(2) = 0.4465) was observed between the expression of MIF and accumulation of CD68-positive macrophages in conjunctiva of patients with OCP. This study demonstrated an increased conjunctival expression of MIF in patients with OCP. MIF may be actively involved in the pathogenesis of OCP, possibly regulating the inflammatory events of the disease process.