Selective immunomodulation in patients with inflammatory bowel disease future therapy or reality ? knowledge of the aetiology and pathogenesis of … (1997 Jan)
selective immunomodulation in patients with inflammatory bowel disease future therapy or reality ? knowledge of the aetiology and pathogenesis of the inflammation in ulcerative colitis and crohn s disease is still insufficient . It is thought that some antigen is the trigger which induces a chain of immune reactions but the origin of this antigen has not so far been elucidated . In theory , an antigen presenting cell forms a complex with endotoxin derived peptides as antigen . T helper lymphocytes recognize this complex , are activated and start to produce cytokines . For inflammatory bowel diseases ( IBD ) the most important cytokines identified are interleukin 1 ( IL 1 ) , interleukin 2 ( IL 2 ) , interleukin 6 ( IL 6 ) , interleukin 8 ( IL 8 ) , gamma interferon ( G IFN ) , and tumor necrosis factor alpha ( TNF alpha ) . inhibition of these cytokines can be achieved by administration of cyclosporine , which inhibits the function of T helper lymphocytes . orally , intravenously , and locally administered cyclosporine is able to improve the disease activity in ulcerative colitis and crohn s disease , but its use is limited because of side effects . The novel immunosuppressant fk506 has comparable actions to cyclosporine in regulating cytokine production and may even be more effective than cyclosporine . The receptor antagonist of IL 1 ( IL 1ra ) competitively binds to the IL 1 receptor located on several lymphocytes . …

Imbalance of the interleukin 1 system in colonic mucosa association with intestinal inflammation and interleukin 1 receptor antagonist corrected genotype … (1998 Jan)
imbalance of the interleukin 1 system in colonic mucosa association with intestinal inflammation and interleukin 1 receptor antagonist corrected genotype 2 . background : interleukin 1 ( IL 1 ) alpha and beta are potent cytokines which play key roles in inflammation . They are controlled by IL 1 receptor antagonist ( IL 1ra ) . AIMS : To investigate the influence of mucosal inflammation and IL 1ra genotype on the IL 1ra : IL 1 balance . patients AND methods : IL 1 alpha , IL 1 beta , and IL 1ra were measured by enzyme linked immunosorbent assay ( elisa ) in biopsy specimens taken from inflamed and non inflamed colon of 60 patients with crohn s disease ( CD ) , 34 with ulcerative colitis ( UC ) , 15 inflammatory controls , and 103 non inflamed controls . IL 1ra genotype was determined by polymerase chain reaction and gel electrophoresis . results : IL 1 alpha and IL 1 beta were significantly increased in inflamed mucosa in inflammatory bowel disease ( IBD ) ( CD : 53 . 5 ( 22 . 4 ) and 409 . 9 ( 118 . 7 ) pg / mg protein , respectively ; UC : 18 . 9 ( 6 . 8 ) and 214 . 5 ( 78 . 2 ) pg / mg , respectively ) and non IBD patients ( 19 . 2 ( 7 . 4 ) and 281 . 4 ( 121 . 0 …

Therapeutic potential of interleukin 1 receptor antagonist in inflammatory bowel disease. (1998 Sep)
therapeutic potential of interleukin 1 receptor antagonist in inflammatory bowel disease . The therapeutic role of interleukin ( IL ) 1 receptor antagonist , a potent inhibitor of IL 1 , was investigated using peripheral blood mononuclear cells from patients with ulcerative colitis and crohn s disease . administration of IL 1 receptor antagonist inhibited IL 1 beta augmented IL 1 alpha and tumor necrosis factor alpha production by mononuclear cells . prednisolone caused a decrease in IL 1 receptor antagonist release , whereas sulfasalazine had no modulatory effect . interestingly , IgG caused an increase in IL 1 receptor antagonist release . In conclusion , IL 1 receptor antagonist and related molecules may have therapeutic value .

In vivo mucosal delivery of bioactive human interleukin 1 receptor antagonist produced by streptococcus gordonii. (2003 Oct)
In vivo mucosal delivery of bioactive human interleukin 1 receptor antagonist produced by streptococcus gordonii . background : interleukin 1 ( IL 1 ) is a cytokine involved in the initiation and amplification of the defence response in infectious and inflammatory diseases . IL 1 receptor antagonist ( IL 1ra ) is an inactive member of the IL 1 family and represents one of the most potent mechanisms for controlling IL 1 dependent inflammation . IL 1ra has proven effective in the therapy of acute and chronic inflammatory diseases in experimental animal models and also in preliminary clinical trials . however , optimisation of therapeutic schedules is still needed . For instance , the use of drug delivery systems targeting specific mucosal sites may be useful to improve topical bioavailability and avoid side effects associated with systemic administration . results : In order to develop systems for the delivery of IL 1ra to mucosal target sites , a streptococcus gordonii strain secreting human IL 1ra was constructed . The recombinant IL 1ra produced by S . gordonii was composed of the four amino acid residues RVFP of the fusion partner at the N terminus , followed by the mature human IL 1ra protein . RFVP / IL 1ra displayed full biological activity in vitro in assays of inhibition of IL 1beta induced lymphocyte proliferation and was released by recombinant S . gordonii in vivo both at the vaginal and the gastrointestinal mucosa of mice . RFVP / IL 1ra appeared …

Soluble tumor necrosis factor receptor 1 and tissue inhibitor of metalloproteinase 1 in hemolytic uremic syndrome with encephalopathy. (2008 Jun)
soluble tumor necrosis factor receptor 1 and tissue inhibitor of metalloproteinase 1 in hemolytic uremic syndrome with encephalopathy . enterohemorrhagic escherichia coli ( EHEC ) induces hemorrhagic colitis and hemolytic uremic syndrome ( HUS ) . morbidity and mortality are increased in HUS patients with neurologic complications . To determine the pathogenesis of the central nervous system ( CNS ) involvement in HUS by EHEC , we determined the serum concentrations of interleukin 6 ( IL 6 ) , tumor necrosis factor alpha ( TNF alpha ) , soluble TNF receptor 1 ( stnfr1 ) , IL 10 , interferon gamma ( IFN gamma ) , IL 2 , IL 4 , soluble E selectin ( sE selectin ) , matrix metalloproteinase 9 ( MMP 9 ) , and tissue inhibitor of metalloproteinase 1 ( TIMP 1 ) during the acute stage in children with HUS with or without CNS involvement . serum concentrations of IL 6 , IL 10 , stnfr1 , sE selectin , MMP 9 , and TIMP 1 , but not TNF alpha , IFN gamma , IL 2 , or IL 4 , were significantly higher in patients with HUS with encephalopathy compared with controls . serum IL 6 , stnfr1 and TIMP 1 concentrations were significantly higher in patients with HUS with encephalopathy compared with those with HUS without encephalopathy ( P 0 . 031 , P 0 . 005 , and P 0 . 007 , respectively ) and those with acute colitis …

Cytokine messenger RNA profiles in inflammatory bowel disease mucosa detected by polymerase chain reaction amplification. (1992 Dec)
cytokine messenger RNA profiles in inflammatory bowel disease mucosa detected by polymerase chain reaction amplification . immunoregulatory properties of cytokines may mediate disordered inflammatory events in ulcerative colitis ( UC ) and crohn s disease ( CD ) . In the present study , profiles of cytokines produced by activated macrophages were studied in colonic tissue from 43 patients with and without inflammatory bowel disease ( IBD ) . cytokine messenger RNA ( mRNA ) extracted from mucosal biopsy specimens was studied using polymerase chain reaction assay techniques . A greater percentage of active UC samples had detectable levels of mRNA for interleukins ( IL ) 1 , 6 , and 8 and gro than samples in inactive UC and noninflammatory controls . these cytokines were comparable in active UC and inflammatory controls . expression of gro mRNA in active UC tissue was significantly higher than in active CD . tumor necrosis factor was detected in only 7 of 43 samples with no difference between groups . active and inactive CD did not differ in percentage of cytokine mRNA expression . IL 1 receptor antagonist ( IL 1ra ) was detected in more inflammatory controls than in CD and was expressed in fewer IBD patients than IL 1 . expression of proinflammatory cytokines in grossly inactive CD and possible defective production of IL 1ra may explain disease reactivation and chronicity .

Adhesion dependent release of hepatocyte growth factor and interleukin 1 receptor antagonist from human blood granulocytes and monocytes : evidence … (2004 Jul)
adhesion dependent release of hepatocyte growth factor and interleukin 1 receptor antagonist from human blood granulocytes and monocytes : evidence for the involvement of plasma IgG , complement C3 and beta2 integrin . objective : evolving evidence of anti inflammatory effects is observed in patients with rheumatoid arthritis or ulcerative colitis following periodic adsorptive granulocyte and monocyte ( GM ) apheresis with a column containing cellulose acetate ( CA ) beads as apheresis carriers . This study was undertaken to obtain insights into mechanisms of anti inflammatory actions of adsorptive GM apheresis with CA beads . methods : In a series of in vitro experiments , we investigated the effects of plasma proteins and the leucocytes beta2 integrin ( CD18 ) on granulocyte adsorption to CA beads . results : granulocyte adsorption to CA beads required plasma IgG , the complement C3 and was inhibited by an antibody to leucocytes CD18 . further , hepatocyte growth factor ( HGF ) and interleukin 1 receptor antagonist ( IL 1ra ) which have strong anti inflammatory actions were released by granulocytes that adhered to CA beads . conclusions : plasma IgG , C3 derived complement activation fragments and leucocytes CD18 are involved in granulocyte adhesion to CA beads and hence the release of HGF and IL 1ra .

Interleukin 1 receptor antagonist : role in biology. (1998 Aug)
interleukin 1 receptor antagonist : role in biology . The interleukin 1 receptor antagonist ( IL 1Ra ) is a member of the IL 1 family that binds to IL 1 receptors but does not induce any intracellular response . Two structural variants of IL 1Ra have previously been described : a 17 kDa form that is secreted from monocytes , macrophages , neutrophils , and other cells ( sIL 1Ra ) and an 18 kDa form that remains in the cytoplasm of keratinocytes and other epithelial cells , monocytes , and fibroblasts ( icIL 1Ra ) . An additional 16 kDa intracellular isoform of IL 1Ra has recently been described in neutrophils , monocytes , and hepatic cells . Both of the major isoforms of IL 1Ra are transcribed from the same gene through the use of alternative first exons . The two promoters regulating transcription of the secreted and intracellular forms have been cloned , and some of the functional cis acting DNA regions have been characterized . The production of IL 1Ra is stimulated by many substances including adherent IgG , other cytokines , and bacterial or viral components . The tissue distribution of IL 1Ra in mice indicates that sIL 1Ra is found predominantly in peripheral blood cells , lungs , spleen , and liver , while icIL 1Ra is found in large amounts in skin . studies in transgenic and knockout mice indicate that IL 1Ra is important in host defense against endotoxin induced injury …

Interleukin 1beta induced production of H2O2 contributes to reduced sigmoid colonic circular smooth muscle contractility in ulcerative colitis. (2004 Sep)
interleukin 1beta induced production of H2O2 contributes to reduced sigmoid colonic circular smooth muscle contractility in ulcerative colitis . We have shown that neurokinin A induced contraction of human sigmoid circular muscle ( HSCM ) is reduced in patients with ulcerative colitis and that interleukin ( IL ) 1beta may play a role in this change . We now examine changes in the signal transduction pathway mediating neurokinin A induced contraction of HSCM and explore the role of IL 1beta and of H ( 2 ) O ( 2 ) in these changes . In Fura 2 AM loaded ulcerative colitis HSCM cells , neurokinin A and caffeine induced peak Ca ( 2 ) increase and cell shortening were significantly reduced . In normal cells , neurokinin A induced contraction was decreased by protein kinase C inhibitor chelerythrine and by calmodulin inhibitor cgs9343b 1 , 3 dihydro 1 1 ( 4 methyl 4H , 6H pyrrolo 1 , 2 a 4 , 1 benzoxazepin 4 yl ) methyl 4 piperidinyl 2H benzimidazol 2 one ( 1 : 1 ) maleate . In ulcerative colitis muscle cells , contraction was inhibited only by chelerythrine but not by cgs9343b . IL 1beta treatment of normal HSCM strips and cells reproduced the changes observed in ulcerative colitis . IL 1beta induced reduction in caffeine induced peak Ca ( 2 ) increase and contraction was reversed by catalase , suggesting a role of H ( 2 ) O ( 2 ) . IL 1beta …

Blocking IL 1 : interleukin 1 receptor antagonist in vivo and in vitro. (1992 Mar)
blocking IL 1 : interleukin 1 receptor antagonist in vivo and in vitro . clinical and experimental evidence suggests that shock , arthritis , osteoporosis , colitis , leukemia , diabetes , wasting and atherosclerosis are mediated , in part , by interleukin 1 ( IL 1 ) . inhibition of this cytokine has been a strategy for studying disease and for new drug development . A naturally occurring IL 1 inhibitor ( IL 1 receptor antagonist , IL 1ra ) that blocks binding of IL 1 to its receptors has been cloned and produced in recombinant organisms . IL 1ra reduces the severity of sepsis , colitis , arthritis and diabetes in animals and is presently being tested in humans with arthritis , shock and myelogenous leukemia .

A neurokinin 1 receptor antagonist reduces an ongoing ileal pouch inflammation and the response to a subsequent inflammatory stimulus. (2003 Nov)
A neurokinin 1 receptor antagonist reduces an ongoing ileal pouch inflammation and the response to a subsequent inflammatory stimulus . ileal pouch anal anastomosis ( IPAA ) is an excellent surgical option for patients with chronic ulcerative colitis ( CUC ) requiring colectomy ; however , persistent episodes of ileal pouch inflammation , or pouchitis , may result in debilitating postoperative complications . because considerable evidence implicates substance P ( SP ) as an inflammatory mediator of CUC , we investigated whether SP participates in the pathophysiology of pouchitis . With the use of a rat model of IPAA that we developed , we showed that ileal pouch MPO levels and neurokinin 1 receptor ( NK 1R ) protein expression by western blot analysis were significantly elevated 28 days after IPAA surgery . In situ hybridization and immunohistochemistry showed that the increase in NK 1R protein expression was localized to the lamina propria and epithelia of pouch ileum . The intraperitoneal administration of the NK 1R antagonist ( NK 1RA ) CJ 12 , 255 for 4 days , starting on day 28 , was effective in reducing MPO levels . starting on day 28 , animals with IPAA were given 5 dextran sulfate sodium ( DSS ) in their drinking water for 4 days , which caused histological and physical signs of clinical pouchitis concomitant with significant increases in ileal pouch MPO concentrations as well as NK 1R protein expression by western blot analysis . In situ hybridization and …

Modulation of cytokine release from colonic explants by bacterial antigens in inflammatory bowel disease. (2003 Jun)
modulation of cytokine release from colonic explants by bacterial antigens in inflammatory bowel disease . The intestinal flora play an important role in experimental colitis and inflammatory bowel disease ( IBD ) . using colonic explant cultures from 132 IBD and control subjects , we examined tumour necrosis factor alpha ( TNF alpha ) , interleukin ( IL ) 1 and interleukin 1 receptor antagonist ( IL 1RA ) production in vitro in response to bacterial activators . unstimulated TNF alpha release was increased significantly in rectal biopsies from involved IBD tissue , correlating with inflammation severity . whereas lipopolysaccharide ( LPS ) only moderately stimulated TNF alpha production from inflamed tissue , pokeweed mitogen ( PWM ) induced its release in all groups , with a stronger response in involved IBD tissue . superantigen staphylococcal enterotoxin A ( SEA ) had a similar , but weaker effect . SEB was observed to be the strongest inducer of TNF alpha for all groups , again with a more marked response in inflamed tissue . stimulated release of IL 1 was considerably less than for TNF alpha . The superantigens superior potency over LPS was not as marked for IL 1 as it was for TNF alpha . In addition to IL 1 , IL 1RA release was also triggered by the bacterial products . The net effect of activation on the IL 1RA / IL 1 ratio was relatively modest . release of the proinflammatory cytokines TNF alpha and IL …

The effect of interleukin 1 beta interleukin 8 in the pathogenesis of experimental colitis and evaluation of interleukin 1 receptor … (2001 Nov)
The effect of interleukin 1 beta interleukin 8 in the pathogenesis of experimental colitis and evaluation of interleukin 1 receptor antagonist therapy objective : To study the effect of interleukin 1 beta and interleukin 8 in the pathogenesis of colitis and evaluate the therapeutic effect of interleukin 1 receptor antagonist ( IL 1ra ) . methods : A rat model of chronic experimental colitis was induced by administration of trinitrobenzenesulfonic acid ( TNBS , 30 mg ) in 50 ethanol 0 . 25 ml . IL 1ra was then administered intravenously with a dosage of 7 mg / kg at different times . hydrocortisone ( 3 mg ) i . v . administration was served as control . tissue expression of IL 1 beta mRNA and IL 8 mRNA was then studied by in situ hybridization before and after IL 1ra administration . histological examination and tissue myeloperoxidase ( MPO ) and superoxide dismutase ( SOD ) activities detection were also made to assess the severity of colitis . results : An acute inflammation with ulcers , neutrophil infiltration and crypt abscess developed that evolved into a chronic inflammation with abundant fibrous connective tissue hypertrophy at 21 days . And it then recurs only after 10 mg TNBS administration . activities of MPO and SOD correlated with severity of inflammation . expression of IL 1 beta mRNA was detected in macrophages in lamina propria and submucosa during the whole period of inflammation . It could be also present in epithelial …

Cytokines in inflammatory bowel disease. (1998 Apr)
cytokines in inflammatory bowel disease . cytokines play a central role in the modulation of the intestinal immune system . They are produced by lymphocytes ( especially T cells of the Th1 and Th2 phenotypes ) , monocytes , intestinal macrophages , granulocytes , epithelial cells , endothelial cells , and fibroblasts . They have proinflammatory functions interleukin 1 ( IL 1 ) , tumor necrosis factor ( TNF ) , IL 6 , IL 8 , IL 12 or antiinflammatory functions interleukin 1 receptor antagonist ( IL 1ra ) , IL 4 , IL 10 , IL 11 , transforming growth factor beta ( TGF beta ) . mucosal and systemic concentrations of many pro and antiinflammatory cytokines are elevated in inflammatory bowel disease ( IBD ) . An imbalance between proinflammatory and antiinflammatory cytokines was found for the IL 1 / IL 1ra ratio in the inflamed mucosa of patients with crohn s disease , ulcerative colitis , diverticulitis , and infectious colitis . furthermore , the inhibition of proinflammatory cytokines and the supplementations with antiinflammatory cytokines reduced inflammation in animal models , such as the dextran sulfate colitis ( DSS ) model , the trinitrobenzene sulfonic acid ( TNBS ) model , or the genetically engineered model of IL 10 knockout mice . based on these findings a rationale for cytokine treatment was defined . The first clinical trials using neutralizing monoclonal antibodies against TNF alpha ( cA2 ) or the antiinflammatory cytokine IL 10 have shown …

Effects of adacolumn selective leukocytapheresis on plasma cytokines during active disease in patients with active ulcerative colitis. (2006 May)
effects of adacolumn selective leukocytapheresis on plasma cytokines during active disease in patients with active ulcerative colitis . AIM : To investigate the relationship between ulcerative colitis ( UC ) clinical activity index ( CAI ) and circulating levels of IL 1ra , IL 10 , IL 6 and IL 18 . methods : blood levels of IL 1ra , IL 10 , IL 6 and IL 18 were measured in 31 patients with active UC , the mean CAI was 11 . 1 , ranging from 5 25 ; and 12 healthy individuals as controls . patients were given granulocyte and monocyte adsorptive apheresis ( GMA ) with adacolumn . leucocytes which bear the fcgammar and complement receptors were adsorbed to the column leucocytapheresis carriers . Each patient could receive up to 11 GMA sessions over 8 wk . results : We found strong correlations between CAI and IL 10 ( r 0 . 827 , P 0 . 001 ) , IL 6 ( r 0 . 785 , P 0 . 001 ) and IL 18 ( r 0 . 791 , P 0 . 001 ) . IL 1ra was not correlated with CAI . following GMA therapy , 24 of the 31 patients achieved remission and the levels of all 4 cytokines fell to the levels in healthy controls . further , blood levels of IL 1ra and IL 10 increased at the column outflow and inflow at 60 min suggesting release from leucocytes that …

Imbalance between interleukin 1 agonists and antagonists : relationship to severity of inflammatory bowel disease. (2004 Oct)
imbalance between interleukin 1 agonists and antagonists : relationship to severity of inflammatory bowel disease . interleukin ( IL ) 1 is a key mediator in the pathogenesis of inflammatory bowel disease ( IBD ) . naturally occurring IL 1 modulators include IL 1 receptor antagonist ( IL 1Ra ) , IL 1 soluble receptor Type I ( IL 1sRI ) , IL 1srii and IL 1 receptor accessory protein ( AcP ) . systemic and mucosal levels of IL 1 soluble receptors remain unknown in IBD . plasma or colonic tissues were obtained from 185 consecutive unselected patients with crohn s disease ( CD ) or ulcerative colitis ( UC ) and from 52 control subjects . plasma and colonic explant culture supernatants were assessed for IL 1alpha , IL 1beta , IL 1Ra , IL 1sRI and IL 1srii . plasma IL 1Ra levels were higher in UC ( 93 ) than in healthy subjects . IL 1alpha and IL 1beta were not detected . IL 1srii levels were marginally lower in CD ( 10 ) and UC ( 9 ) , whereas IL 1sRI levels were elevated in CD ( 28 ) only . plasma IL 1sRI levels correlated positively ( P 0 . 01 ) with crohn s disease activity index ( r 0 . 53 ) , C reactive protein ( r 0 . 46 ) and alpha1 acid glycoprotein ( r 0 . 42 ) . In colonic explant cultures , IL 1alpha and …

Interleukin 1beta gene in esophageal , gastric and colorectal carcinomas. (2007 Jul)
interleukin 1beta gene in esophageal , gastric and colorectal carcinomas . interleukin ( IL ) 1 gene polymorphisms are associated with development of gastric atrophy and with increased risk of gastric carcinoma . A 31C to T base transition in the promoter region of this gene is involved in carcinogenic changes within the stomach , especially in helicobacter pylori infected individuals . We examined association between IL 1 locus polymorphisms and risk of esophageal , gastric and colorectal carcinomas in japanese patients with H . pylori infection . IL 1B and IL 1RN polymorphisms were analyzed in 136 controls , 75 patients with esophageal carcinoma , 186 patients with gastric carcinoma , 69 patients with colorectal carcinoma , and 18 patients with ulcerative colitis ( UC ) . For IL 1B 511 and 31 polymorphisms were determined by fluorescence based polymerase chain reaction single strand conformation polymorphism analysis . For IL 1 receptor antagonist gene ( IL 1RN ) , penta allelic variable number of tandem repeats ( VNTR ) was determined by PCR standard agarose gel electrophoresis . For gastric carcinoma , IL 1B 511 heterozygotes ( OR , 0 . 48 ; 95 CI , 0 . 3 0 . 9 ; p 0 . 0115 ) and T carriers ( OR , 0 . 52 ; 95 CI , 0 . 3 1 . 0 ; p 0 . 0185 ) had a significantly reduced risk of carcinoma . For colorectal carcinoma , IL 1B 511 heterozygotes …

A simple filter paper technique allows detection of mucosal cytokine levels in vivo in ulcerative colitis. (1996 Oct)
A simple filter paper technique allows detection of mucosal cytokine levels in vivo in ulcerative colitis . interleukin 1 and interleukin 1 receptor antagonist . A simple filter paper method for in vivo assessment of cytokines in intestinal mucosa of patients with ulcerative colitis ( UC ) was developed and evaluated . twenty eight patients were included . twenty three patients had ulcerative colitis ( UC ) and five irritable bowel syndrome ( IBS ) . inflammation was assessed endoscopically . through a rectoscope , filter paper was applied to the macroscopically most inflamed area of the rectal mucosa until soaked . The filter paper was transferred to a buffer solution , and IL 1 beta and IL 1ra were assessed using elisa . positive correlations between endoscopic grading and In ( IL 1 beta ) ( P 0 . 0001 ) and In ( IL 1ra ) ( P 0 . 001 ) and a negative correlation between endoscopic grading and In ( IL 1ra / IL 1 beta ) ( P 0 . 02 ) were found . In measurements during and after a flare up no significant change in IL 1ra but a significant decrease in IL 1 beta was detected , which is in agreement with investigations on biopsies . In conclusion , the filter paper technique is an easily applicable , low risk method that provides a means of monitoring cytokines in vivo in UC .

Immunoregulatory role of interleukin 10 in patients with inflammatory bowel disease. (1995 May)
immunoregulatory role of interleukin 10 in patients with inflammatory bowel disease . background / AIMS : active inflammatory bowel disease ( IBD ) is associated with increased proinflammatory cytokines . deficiency of interleukin ( IL ) 10 , a contrainflammatory cytokine , leads to the development of colitis in IL 10 knockout mice . We characterized IL 10 regulation of proinflammatory cytokine ( tumor necrosis factor TNF alpha and IL 1 beta ) expression in IBD in vitro and in vivo . methods : IL 10 regulation of IL 1 beta , TNF alpha , and IL 1 receptor antagonist expression by peripheral monocytes or isolated lamina propria mononuclear cells ( lpmnc ) , respectively , was studied by enzyme linked immunosorbent assay ( cytokine secretion ) and by semiquantitative reverse transcription polymerase chain reaction . results : IL 10 down regulates IL 1 beta and TNF alpha secretion as well as messenger RNA levels in IBD peripheral monocytes and lpmnc in a dose dependent manner . In parallel , IL 1 receptor antagonist secretion is induced , and IL 10 can restore diminished in vitro IL 1 receptor antagonist / IL 1 beta ratios in IBD to normal levels . equal concentrations of IL 10 are detectable in both normal and IBD intestinal lamina propria biopsy homogenates . after topical IL 10 enema treatment of three steroid therapy refractory patients with ulcerative colitis , in vitro release of proinflammatory cytokines from IBD peripheral monocytes as well as lpmnc is …

Cytokine gene polymorphisms in turkish patients with inflammatory bowel disease. (2006 Apr)
cytokine gene polymorphisms in turkish patients with inflammatory bowel disease . objective : crohn s disease ( CD ) and ulcerative colitis ( UC ) are chronic inflammatory diseases of the bowel , the causes of which are not fully known . ethnic differences in disease prevalence , familial aggregation of the disease and studies of twins provide the most important evidence to suggest that genetic factors play a role in the pathogenesis of inflammatory bowel disease ( IBD ) . The aim of this study was to examine the allelic polymorphisms that can determine the immune response levels in tumor necrosis factor alpha ( tnfalpha ) , interleukin 1beta ( IL 1B ) , interleukin 1 receptor antagonist ( IL 1RN ) and interleukin 10 ( IL 10 ) genes and to investigate their roles in the inflammatory pathway in IBD . material AND methods : The study included 120 patients with UC and 70 patients with CD who were diagnosed either endoscopically or histopathologically . The control group comprised 105 healthy individuals who stated that they had never had any bowel disease during their life span . The polymerase chain reaction restriction fragment length polymorphism ( PCR RFLP ) method for polymorphisms in the tnfalpha gene at positions 308 and 238 , the IL 10 gene at positions 1082 and 627 , the IL 1B gene at 511 regions and the variable number of tandem repeat ( VNTR ) method for polymorphism in the intron 2 of the …