Macrophage migration inhibitory factor in the sera and at the colonic mucosa in patients with ulcerative colitis : clinical implications … (2001 Apr)
macrophage migration inhibitory factor in the sera and at the colonic mucosa in patients with ulcerative colitis : clinical implications and pathogenic significance . background : inflammatory cytokines produced by activated macrophages are implicated in the pathogenesis of ulcerative colitis ( UC ) . With the theory that macrophage migration inhibitory factor ( MIF ) may have a role in the accumulation of macrophages , we studied MIF in UC . materials AND methods : A total of 27 patients with UC , 14 patients with crohn s diseases ( CD ) , 11 patients with other forms of colitis and 26 normal controls were enrolled in the study . The levels of MIF in the sera and culture supernatant were measured by an enzyme linked immunosorbent assay . MIF , macrophages and T cells were localized at the colonic mucosa by immunohistochemistry . results : The levels of MIF in the sera were significantly higher in UC than in normal controls ( P 0 . 05 ) , in serum C reactive protein ( CRP ) positive cases with UC than in CRP negative cases with UC ( P 0 . 05 ) , and in patients with severe colitis with UC than in mild colitis with UC ( P 0 . 05 ) . there was a positive relationship between serum MIF levels with the CRP levels and activities of colitis . however , the levels of MIF in patients with CD and other forms of colitis were …

Human thioredoxin 1 ameliorates experimental murine colitis in association with suppressed macrophage inhibitory factor production. (2006 Oct)
human thioredoxin 1 ameliorates experimental murine colitis in association with suppressed macrophage inhibitory factor production . background AIMS : thioredoxin 1 ( TRX ) is a small multifunctional protein with antioxidative and redox regulating functions . In this study , we investigated the significance of TRX in patients with inflammatory bowel disease ( IBD ) and the ability and mechanism to ameliorate experimental colitis . methods : serum TRX and macrophage migration inhibitory factor ( MIF ) levels were measured in patients with IBD . The effects of TRX were evaluated in a dextran sulfate sodium ( DSS ) induced colitis model by comparing TRX overexpressing transgenic ( TRX TG ) and control mice . We further evaluated the effect of recombinant human TRX ( rhtrx ) administration on DSS induced colitis and colonic inflammation of interleukin ( IL ) 10 knockout ( IL 10 KO ) mice . colonic inflammation was examined clinically and histologically . proinflammatory cytokine levels were examined in colonic tissues , and MIF levels were measured in colonic tissues and sera in mice . The effect of TRX on MIF production was also analyzed in vitro . results : serum TRX and MIF levels were significantly higher in patients with IBD than normal controls , and TRX levels correlated with disease activity . TRX significantly ameliorated DSS induced colitis and colonic inflammation of IL 10 KO mice . increase of tumor necrosis factor alpha and interferon gamma in colonic tissues was significantly suppressed in TRX …

Pathophysiological roles of macrophage migration inhibitory factor in gastrointestinal , hepatic , and pancreatic disorders. (2005 Mar)
pathophysiological roles of macrophage migration inhibitory factor in gastrointestinal , hepatic , and pancreatic disorders . macrophage migration inhibitory factor ( MIF ) is a unique protein , participating in inflammation , immune response , and cell growth . MIF was first discovered as a lymphokine involved in delayed hypersensitivity and various macrophage functions , including phagocytosis , spreading , and tumoricidal activity . It has been reported that MIF is associated with the pathogenesis of a variety of diseases . MIF expression was increased at inflammatory sites in diseases such as rheumatoid arthritis and glomerulonephritis . In experimental inflammatory disease , blockade of MIF bioactivity inhibited the severity of disease activity . On the other hand , MIF expression is also increased in tumor lesions , and MIF plays a role as a cell growth factor . MIF has been reported to be constitutively expressed in gut , liver , and pancreas . In patients with gastritis , inflammatory bowel disease , hepatitis , and pancreatitis , MIF expression was remarkably increased in both the serum and the local lesions . blockade of MIF bioactivity inhibited and prevented inflammation in experimental gastritis , colitis , hepatitis , and pancreatitis . On the other hand , MIF expression was higher than that in normal tissues in colonic carcinomas and hepatocellular carcinoma both in vivo and in vitro . blockade of MIF bioactivity successfully inhibited tumor cell growth in vivo and in vitro . MIF plays important roles in the pathogenesis …

Sex steroid regulation of macrophage migration inhibitory factor in normal and inflamed colon in the female rat. (2007 Mar)
Sex steroid regulation of macrophage migration inhibitory factor in normal and inflamed colon in the female rat . background AND AIMS : Sex steroids influence IBD symptoms . macrophage migration inhibitory factor ( MIF ) , a target of sex steroids in other inflammatory models , promotes interleukin ( IL ) 1beta and tumor necrosis factor ( TNF ) alpha release in colitis . We investigated whether estradiol and progesterone influence MIF , IL 1beta , and TNF alpha production in experimental colitis . methods : colonic MIF , IL 1beta , and TNF alpha levels were measured in cyclic and ovariectomized rats , with or without estradiol benzoate ( EB ) or progesterone ( P ) replacement . MIF distribution was assessed by immunohistochemistry . cytokines , myeloperoxidase activity , macroscopic damage , and plasma corticosterone were assessed 24 hours after intrarectal trinitrobenzene sulfonic acid ( TNBS ) , with and without neutralizing anti MIF antibody . effects of EB and P on myeloperoxidase activity and MIF concentration were also assessed at 7 days in dextran sulfate sodium induced colitis . results : basal IL 1beta and TNF alpha contents did not fluctuate during the estrous cycle , while MIF concentrations increased from estrus ( estrogen dominance ) to metestrus ( P dominance ; P . 05 ) . EB and P treatment mimicked these effects in ovariectomized rats , and similarly altered MIF immunostaining . progesterone dominance aggravated TNBS colitis in comparison with estrogen . progesterone enhanced TNBS …

Glucocorticoid counter regulation : macrophage migration inhibitory factor as a target for drug discovery. (2001 Dec)
glucocorticoid counter regulation : macrophage migration inhibitory factor as a target for drug discovery . Over the past year , human studies have confirmed and expanded the involvement of macrophage migration inhibitory factor ( MIF ) in a number of diseases that had originally been studied in animals . In addition to sepsis , rheumatoid arthritis , glomerulonephritis and inflammatory lung disease , elevated MIF levels have been described in patients suffering from ulcerative colitis , inflammatory neurological diseases and cancer . cellular studies indicate that in addition to macrophages , MIF affects the activities of CD4 and CD8 T cells , natural killer cells , fibroblasts and endothelial cells , actions that may explain the contribution of MIF to inflammatory diseases and cancer . molecular studies have identified direct interactions between MIF and several intracellular regulatory proteins ( Jab1 , PAG and p53 ) that control cellular growth and proliferation ; however , how interactions with these proteins fit into a general scheme to explain MIF s biological activity has not been elucidated . The three dimensional structure of MIF has offered some surprising clues and if the potential enzymatic sites identified are involved with MIF associated diseases , they may provide good targets for therapeutic intervention .

Development of chronic colitis is dependent on the cytokine MIF. (2001 Oct)
development of chronic colitis is dependent on the cytokine MIF . The cytokine macrophage migration inhibitory factor ( MIF ) is secreted by a number of cell types upon induction by lipopolysaccharide ( LPS ) . because colitis is dependent on interplay between the mucosal immune system and intestinal bacteria , we investigated the role of MIF in experimental colitis . MIF deficient mice failed to develop disease , but reconstitution of MIF deficient mice with wild type innate immune cells restored colitis . In addition , established colitis could be treated with anti MIF immunoglobulins . Thus , murine colitis is dependent on continuous MIF production by the innate immune system . because we found increased plasma MIF concentrations in patients with crohn s disease , these data suggested that MIF is a new target for intervention in crohn s disease .

Resistance to experimental colitis depends on cytoprotective heat shock proteins in macrophage migration inhibitory factor null mice. (2006 Nov)
resistance to experimental colitis depends on cytoprotective heat shock proteins in macrophage migration inhibitory factor null mice . macrophage migration inhibitory factor plays an important role in inflammatory diseases . We investigated the role of macrophage migration inhibitory factor ( MIF ) in the development of dextran sulfate sodium ( DSS ) induced colitis using MIF null ( ( / ) ) mice . MIF ( / ) mice given 3 DSS showed no clinical and histological feature of colitis in contrast to wild type ( WT ) mice . Lack of MIF suppressed the up regulation of TNF alpha and IFN gamma as Th1 derived cytokines , and increased the level of IL 4 as Th2 derived cytokine in the colon tissues . moreover , we found that the expressions of heat shock protein ( HSP ) 40 and hsp70 were markedly up regulated in the colon of MIF ( / ) mice in response to DSS compared with WT mice . additionally , quercetin , an inhibitor of HSP synthesis , inhibited the up regulation of hsp40 and 70 expressions and developed DSS induced colitis in MIF ( / ) mice . Our findings in this study provide more information in the role of MIF in colitis .

The role of macrophage migration inhibitory factor ( MIF ) for dextran sulfate sodium induced colitis in mice (2001 Aug)
The role of macrophage migration inhibitory factor ( MIF ) for dextran sulfate sodium induced colitis in mice

Macrophage migration inhibitory factor : gene polymorphisms and susceptibility to inflammatory diseases. (2005 Oct)
macrophage migration inhibitory factor : gene polymorphisms and susceptibility to inflammatory diseases . The cytokine macrophage migration inhibitory factor ( MIF ) is a constitutive element of the host antimicrobial defenses and stress response that promotes proinflammatory function of the innate and acquired immune systems . MIF plays an important role in the pathogenesis of acute and chronic inflammatory or autoimmune disorders , such as sepsis , acute respiratory distress syndrome , asthma , rheumatoid arthritis , and inflammatory bowel diseases . polymorphisms of the human MIF gene ( that is , guanine to cytosine transition at position 173 or CATT tetranucleotide repeat at position 794 ) have been associated with increased susceptibility to or severity of juvenile idiopathic and adult rheumatoid arthritis , ulcerative colitis , atopy , or sarcoidosis . whether these MIF polymorphisms affect the susceptibility to and outcome of sepsis has not yet been examined . analyses of MIF genotypes in patients with sepsis may help to classify patients into risk categories and to identify those patients who may benefit from anti MIF therapeutic strategies .

Macrophage migration inhibitory factor has a proinflammatory activity via the p38 pathway in glucocorticoid resistant ulcerative colitis. (2006 Aug)
macrophage migration inhibitory factor has a proinflammatory activity via the p38 pathway in glucocorticoid resistant ulcerative colitis . macrophage migration inhibitory factor ( MIF ) is a cytokine that has potent anti steroid effects and might be implicated in the pathogenesis of ulecrative colitis ( UC ) . We defined the functional role of MIF in the glucocorticoid ( GC ) resistant inflammatory response in UC . twenty four colonic samples were obtained from GC responsive cases , GC refractory cases , crohn s disease and controls . LPMC were isolated from surgical specimens . MIF was strongly expressed at mRNA levels in refractory cases rather than responsive cases with UC and controls . IL 8 production from LPMC was significantly reduced by GC addition in responsive cases but not in refractory cases . In refractory cases , anti MIF Ab ameliorated GC resistant IL 8 production and p38 MAPK activity of LPMC . In addition , p38 MAPK antagonist sb230580 also ameliorated GC resistant IL 8 production . these results suggest that MIF has an additional proinflammatory activity through the p38 MAPK pathway in GC resistant UC .

Comparison of two lymphokines ( macrophage migration inhibition , leukocyte adherence inhibition factors ) and carcinoembryonic antigen , in colorectal … (1988 Jan)
comparison of two lymphokines ( macrophage migration inhibition , leukocyte adherence inhibition factors ) and carcinoembryonic antigen , in colorectal cancer and colonic premalignant lesions . previous studies in our laboratory on 92 patients with colonic cancer have suggested a promising degree of specificity and sensitivity for a macrophage migration inhibition factor ( MIF ) test using patient s lymphocytes incubated with a human colon cancer extract . This study compares the results of the MIF technique with serum carcinoembryonic antigen ( CEA ) levels and with the lymphocyte adherence inhibition ( LAI ) test in 18 colon cancer patients and 27 patients with conditions considered to predispose to colon cancer ( colonic adenomas , ulcerative colitis , and crohn s disease ) . among colonic cancer patients , MIF and LAI were positive in 17 out of 18 , but CEA was elevated in eight . MIF and CEA were negative in all 16 normal control subjects ; LAI was negative in 13 . among patients with colonic adenomas , MIF and LAI were positive in three of five ; CEA was negative in all . In the ulcerative colitis and crohn s disease group , MIF was positive in seven of 22 , LAI was positive in 11 , and CEA was negative in all 22 . Thus , MIF and LAI appear to be sensitive marker s for human colonic cancer . More extensive studies and precise characterization of these groups are warranted .

New therapeutic target in inflammatory disease : macrophage migration inhibitory factor. (2005 Jun)
New therapeutic target in inflammatory disease : macrophage migration inhibitory factor . The cytokine macrophage migration inhibitory factor ( MIF ) participates in fundamental events in innate and adaptive immunity . The profile of activities of MIF in vivo and in vitro is strongly suggestive of a role for MIF in the pathogenesis of many inflammatory diseases , including rheumatoid arthritis ( RA ) , and hence antagonism of MIF is suggested as a potential therapeutic strategy in inflammatory disease . The best developed case for therapeutic antagonism of MIF is in RA . In RA , MIF is abundantly expressed in serum and synovial tissue . MIF induces synovial expression of key pro inflammatory genes , regulates the function of endothelial cells and leucocytes , and is implicated in the control of synoviocyte proliferation and apoptosis via direct effects on the expression of the tumour suppressor protein p53 . In animal models of RA , anti MIF antibodies or genetic MIF deficiency are associated with significant inhibition of disease . A similar case has been made , for example using MIF deficient mice , in models of atheroma , colitis , multiple sclerosis and other inflammatory diseases . The relationship with p53 also means MIF may be important in the link between inflammatory disease and cancer , such as is seen in RA or colitis . MIF also has a unique relationship with glucocorticoids , in that despite antagonizing their effects , the expression of MIF is in fact …

Association of the 173 G / C polymorphism of the macrophage migration inhibitory factor gene with ulcerative colitis. (2004 Apr)
association of the 173 G / C polymorphism of the macrophage migration inhibitory factor gene with ulcerative colitis . background : macrophage migration inhibitory factor ( MIF ) is a proinflammatory cytokine and has been shown to be involved in the development of chronic murine colitis . In the 173 G / C polymorphism of the MIF gene , the presence of C creates the binding motif of activator protein 4 . This study explored the association of this polymorphism with ulcerative colitis ( UC ) . methods : genotyping was carried out , with a tetra primer polymerase chain reaction ( PCR ) method , for 659 DNA specimens from 438 healthy volunteers and 221 patients with UC . genotype distribution between cases and controls and the association of patients genotypes with clinical parameters were statistically evaluated . results : No significant difference in genotype distribution was found between UC patients and healthy controls . however , when the relation of the C / C genotype to clinical parameters in UC patients was evaluated by fisher s exact test , it was found that the frequency of the C / C genotype was higher in patients with pancolitis type than in those with other types restricted to the distal or left sided colon ( odds ratio OR , 10 . 781 ; 95 confidence interval CI , 1 . 342 86 . 619 ; P 0 . 0074 ) . conclusions : these data suggest that the MIF 173 …

Migration inhibitory factor is involved in experimental colitis induced by intrathecal injection of haptten to rat. (2008 Jun)
migration inhibitory factor is involved in experimental colitis induced by intrathecal injection of haptten to rat . In recent years , there has emerged academic tendency towards the neurogenic mechanism of ulcerative colitis ( UC ) . As one of the supports to the hypothesis of UC being a neurogenic inflammation , we have built a colitis model by intrathecal ( ith ) injection of a haptten 2 , 4 dinitrochlorobenzene ( DNCB ) to DNCB sensitized rats . In order to explore further the neuroimmunal mechanism of this colitis model , we here focused on a pro inflammatory cytokine , migration inhibitory factor ( MIF ) , to observe its expression in rat colon nervous tissue and spinal cord in the colitis induced by ith injection of DNCB . At the same time we also observed the effect of MIF antibody pretreatment on the disease active index ( DAI ) score and the colon pathology by HE staining in the colitis rats . The results obtained showed that the immunofluorescence intensity of double staining of MIF protein in colon nervous tissue and spinal cord was increased in 0 . 8 and 1 . 6 DNCB induced colitis groups than that in the control ( 60 ethanol ) group . Both the colon pathology and the DAI score were significantly reduced by MIF antibody ith pretreatment . Ith injection of 0 . 8 DNCB after MIF antibody ( 1 : 10 , 1 : 5 ) pretreatment could only induce …

Newer uses of glucose insulin potassium regimen. (2001 Mar)
newer uses of glucose insulin potassium regimen . diabetic ketoacidosis and moderate degree of hyperglycemia can be managed by glucose insulin potassium ( GIK ) regimen . The GIK regimen is also useful in the treatment of acute myocardial infarction ( AMI ) . But , the exact mechanism ( s ) of the beneficial action of GIK regimen is not known . I suggest that glucose insulin can suppress the secretion and antagonize the harmful effects of tumor necrosis factor alpha ( TNF alpha ) and macrophage migration inhibitory factor ( MIF ) . If this is true , it suggests that GIK regimen may be useful in septicemia and septic shock , and other inflammatory conditions such as ulcerative colitis , crohn s disease , rheumatoid arthritis , systemic lupus erythematosus and cancer , conditions in which TNF alpha and MIF appear to play a major role .

Association of MIF 173 gene polymorphism with inflammatory bowel disease in chinese Han population. (2008 Jan)
association of MIF 173 gene polymorphism with inflammatory bowel disease in chinese Han population . AIM : To study whether macrophage migration inhibitory factor ( MIF ) 173 gene polymorphism correlates with inflammatory bowel disease ( IBD ) in chinese Han population . methods : MIF 173 single nucleotide polymorphism ( SNP ) was genotyped by tetra primer amplification refractory mutation system ( ARMS ) and restriction fragment length polymorphisms ( RFLP ) PCR in 142 healthy subjects and 98 patients with inflammatory bowel disease ( IBD ) . results : there were no discrepancies between the results obtained by tetra primer ARMS and RFLP PCR . The frequency of MIF 173 CC genotype was significantly higher in patients with ulcerative colitis ( UC ) 15 . 5 than in healthy individuals 5 . 6 ( chi ( 2 ) 6 . 066 , P 0 . 018 , OR 3 . 067 and 95 CI 1 . 257 7 . 482 ) . there was a trend towards a higher frequency of CC genotype among CD patients compared with healthy controls , however this did not attain the statistical significance ( P 0 . 245 ) . conclusion : MIF 173 CC genotype may be associated with susceptibility to UC .

Macrophage migration inhibitory factor contributes to the development of acute dextran sulphate sodium induced colitis in Toll like receptor 4 … (2005 Jul)
macrophage migration inhibitory factor contributes to the development of acute dextran sulphate sodium induced colitis in Toll like receptor 4 knockout mice . Toll like receptor 4 ( TLR4 ) , which recognizes lipopolysaccharides , plays an important role in the innate immune response . In this study , we investigated the role of TLR4 in the development of experimental colitis with regard to the biological actions of macrophage migration inhibitory factor ( MIF ) using TLR4 null ( ( / ) ) mice . TLR4 ( / ) mice were given 2 dextran sulphate sodium ( DSS ) in drinking water to induce colitis , which was clinically and histologically as severe as that seen in wild type ( WT ) mice . The level of tumour necrosis factor ( TNF ) alpha in colon tissues was increased in WT mice but unchanged in TLR4 ( / ) mice . The level of myeloperoxidase ( MPO ) activity in colon tissues was increased by DSS administration in both TLR4 ( / ) and WT mice . The expression of MIF was up regulated in the colons of TLR4 ( / ) mice with acute DSS induced colitis . An anti MIF antibody significantly suppressed colitis and elevation of matrix metalloproteinase 13 in TLR4 ( / ) mice . The current results obtained from TLR4 ( / ) mice provide evidence that MIF plays a critical role in the development of acute DSS induced colitis .

A polymorphism in the macrophage migration inhibitory factor gene is involved in the genetic predisposition of crohn s disease and … (2007 Jun)
A polymorphism in the macrophage migration inhibitory factor gene is involved in the genetic predisposition of crohn s disease and associated with cumulative steroid doses . background / AIMS : macrophage migration inhibitory factor ( MIF ) is an important cytokine involved in the regulation of the innate immune system in IBD . secreted MIF is able to induce the production of pro inflammatory cytokines and counteracts anti inflammatory effects of steroids . We evaluated whether the single nucleotide polymorphism ( SNP ) G / C at position 173 of the MIF gene contributes to the predisposition to IBD and higher amounts of steroid therapy . methodology : We genotyped the SNP G / C at position 173 of the MIF gene in 157 patients with crohn s disease ( CD ) , 102 patients with ulcerative colitis ( UC ) and 489 healthy controls . allele frequencies and cumulative steroid doses were compared . results : C allele and CC genotype frequencies were significantly decreased in CD patients compared to controls ( p 0 . 012 and p 0 . 022 , respectively ) . No significant differences were found in UC patients compared to controls . cumulative corticosteroid dose was significantly higher in CD patients with the CC genotype 12300mg / yr ( 0 40000mg / yr ) , p 0 . 021 compared with the GC genotype 220mg / yr ( 0 450mg / yr ) and the GG genotype ( 310mg / yr ( 100 500mg …

Macrophage migration inhibitory factor and activator protein 1 in ulcerative colitis. (2005 Jan)
macrophage migration inhibitory factor and activator protein 1 in ulcerative colitis . macrophage migration inhibitory factor ( MIF ) is a cytokine that has potent antisteroid effects . We determined that MIF is involved in the glucocorticoid resistant inflammatory process of ulcerative colitis ( UC ) , and the altered AP 1 signal is a potent therapeutic target for refractory UC .

Amelioration of dextran sulfate sodium induced colitis by anti macrophage migration inhibitory factor antibody in mice. (2002 Jul)
amelioration of dextran sulfate sodium induced colitis by anti macrophage migration inhibitory factor antibody in mice . background AIMS : We investigated the effects of macrophage migration inhibitory factor ( MIF ) antibodies in experimental colitis induced dextran sulfate sodium ( DSS ) and trinitrobenzenesulfonic acid ( TNBS ) and examined whether plasma levels of MIF were elevated in patients with inflammatory bowel disease ( IBD ) . methods : BALB / c or c57bl / 6 mice were fed 4 DSS in their drinking water for up to 7 days with and without administration of an anti MIF antibody every 2 days . The severity of inflammation in the cecum and colon was assessed by clinical signs and histologic scoring . tissue levels of MIF , tumor necrosis factor ( TNF ) alpha , interferon gamma ( IFN gamma ) , interleukin ( IL ) 4 , and matrix metalloproteinase ( MMP ) 13 messenger RNA ( mRNA ) were measured . The effects of anti MIF antibody on chronic colitis induced by TNBS was assessed in BALB / c mice . plasma MIF concentrations were assayed in patients with crohn s disease , ulcerative colitis , and healthy controls . results : during DSS induced colitis , colonic MIF mRNA expression was increased . clinical signs and histopathologic features were significantly improved in animals given anti MIF antibody . DSS induced up regulation of colonic TNF alpha and IFN gamma were significantly suppressed in animals given the anti …