Opposing roles for IL 13 and IL 13 receptor alpha 2 in health and disease. (2004 Nov)
opposing roles for IL 13 and IL 13 receptor alpha 2 in health and disease . interleukin ( IL ) 13 is a key inducer of several type 2 cytokine dependent pathologies . It regulates inflammation , mucus production , tissue remodeling , and fibrosis . consequently , it has become an important therapeutic target for a number of debilitating illnesses , including asthma , idiopathic pulmonary fibrosis , ulcerative colitis , as well as several other diseases in which IL 13 is believed to be overproduced . In the murine model of schistosomiasis , IL 13 has emerged as a central mediator of chronic infection induced liver pathology . although IL 4 , IL 5 , IL 10 , and IL 13 each regulate distinct aspects of the granulomatous inflammatory response , IL 13 was identified as the primary mediator of liver fibrosis . Thus , elucidating the mechanisms that regulate the production and function of IL 13 has become an intensive area of research . IL 13 signaling is mediated by the type 2 IL 4 receptor , which consists of the IL 4R alpha and IL 13R alpha 1 chains . however , another IL 13 binding chain , IL 13R alpha 2 , appears to strongly inhibit the activity of IL 13 . animals deficient in IL 13R alpha 2 fail to downmodulate granuloma formation in the chronic phase of infection . They also develop severe IL 13 dependent fibrosis and portal hypertension and quickly succumb …

Tolerance to endotoxin induced expression of the interleukin 1 beta gene in blood neutrophils of humans with the sepsis syndrome. (1993 Apr)
tolerance to endotoxin induced expression of the interleukin 1 beta gene in blood neutrophils of humans with the sepsis syndrome . The induction of genes of host cells stimulated by microbial products such as endotoxin and the tolerance of cells to endotoxin excitation play critical roles in the pathogenesis of microbial induced acute disseminated inflammation with multiorgan failure ( the sepsis syndrome ) . One gene that is induced in phagocytic cells by endotoxin and that appears to play an essential role in the pathogenesis of the sepsis syndrome is IL 1 beta . We report here that blood neutrophils ( PMN ) of patients with the sepsis syndrome ( sepsis PMN ) are consistently tolerant to endotoxin induced expression of the IL 1 beta gene , as determined by decreased synthesis of the IL 1 beta protein and reductions in IL 1 beta mRNA . This down regulation of the IL 1 beta gene in sepsis PMN occurs concomitant with an upregulation in the constitutive expression of the type 2 IL 1 receptor ( IL 1R2 ) . these phenotypic changes do not persist in PMN of patients recovering from the sepsis syndrome . tolerance has stimulus and response specificity since sepsis PMN tolerant to endotoxin can respond normally to staphylococcus aureus stimulation of IL 1 beta production and they normally secrete elastase . uninfected patients with severe trauma or shock from causes are not tolerant to endotoxin and tolerance is not limited to patients infected with Gram negative …

Tissue interleukin 1 and interleukin 1 receptor antagonist expression in enterocolitis in resistant and susceptible rats. (1994 May)
tissue interleukin 1 and interleukin 1 receptor antagonist expression in enterocolitis in resistant and susceptible rats . background / AIMS : subserosal injection of purified group A streptococcal peptidoglycan polysaccharide ( PG APS ) induces chronic relapsing granulomatous enterocolitis and systemic inflammation in susceptible inbred lewis rats but only transient intestinal injury in buffalo and fischer rats . cecal interleukin 1 ( IL 1 ) and IL 1 receptor antagonist ( IL 1ra ) expression was measured in inbred rats displaying differential susceptibility to experimental enterocolitis . methods : The ileum and cecum of lewis , buffalo , and fischer rats were subserosally injected with purified PG APS or albumin . IL 1 and IL 1ra messenger RNA ( mRNA ) and protein ( IL 1 only ) were measured 1 or 27 days later . PG APS injected lewis rats were treated with recombinant human IL 1ra . kinetics of IL 1 and IL 1ra mRNA expression were studied in peritoneal cells . results : All rats strains developed acute inflammation with increased cecal concentrations of IL 1 beta and IL 1ra mRNA . lewis rats developed chronic enterocolitis and had higher IL 1 and IL 1ra mRNA tissue levels than buffalo or fischer rats , which displayed no chronic inflammation . IL 1 beta and IL 1ra were produced by submucosal granulomas and correlated with inflammation . IL 1 alpha protein levels paralleled IL 1 beta mRNA expression . IL 1ra treatment attenuated acute and chronic enterocolitis , …

Signaling by IL 12 and IL 23 and the immunoregulatory roles of stat4. (2004 Nov)
signaling by IL 12 and IL 23 and the immunoregulatory roles of stat4 . produced in response to a variety of pathogenic organisms , interleukin ( IL ) 12 and IL 23 are key immunoregulatory cytokines that coordinate innate and adaptive immune responses . these dimeric cytokines share a subunit , designated p40 , and bind to a common receptor chain , IL 12R beta 1 . The receptor for IL 12 is composed of IL 12R beta 1 and IL 12R beta 2 , whereas IL 23 binds to a receptor composed of IL 12R beta 1 and IL 23R . Both cytokines activate the janus kinases Tyk2 and Jak2 , the transcription factor signal transducer and activator of transcription 4 ( stat4 ) , as well as other stats . A major action of IL 12 is to promote the differentiation of naive CD4 T cells into T helper ( Th ) 1 cells , which produce interferon ( IFN ) gamma , and deficiency of IL 12 , IL 12R subunits or stat4 is similar in many respects . In contrast , IL 23 promotes end stage inflammation . targeting IL 12 , IL 23 , and their downstream signaling elements would therefore be logical strategies for the treatment of immune mediated diseases .

Identification of IL 1 inhibitory activity as IL 1 receptor antagonist ( IL 1ra ) in vitro and kinetics of … (1995 Jul)
identification of IL 1 inhibitory activity as IL 1 receptor antagonist ( IL 1ra ) in vitro and kinetics of IL 1ra and IL 1 beta in experimental rabbit lung granuloma . This study investigated whether interleukin 1 ( IL 1 ) inhibitory activity in LPS stimulated culture supernatants of alveolar macrophages and epithelioid cells obtained from rabbit lung granulomas induced by complete freund s adjuvant ( CFA ) was identical to IL 1 receptor antagonist ( IL 1ra ) and examined the changes of IL 1ra and IL 1 beta levels in lung tissue during the natural course of granulomatous inflammation . In the thymocyte proliferation assay , prostaglandin E2 ( PGE2 ) free culture supernatants from each cell population revealed a bell shaped IL 1 titration curve with IL 1 activity suppressed at dilutions of 1 : 1 to 1 : 2 , and gel chromatography of serum free culture supernatants showed an IL 1 inhibitory peak at 21 25 kD . suppression of IL 1 activity in the supernatants at lower dilutions and the gel purified IL 1 inhibitory activity both almost disappeared after IL 1ra depletion with an anti rabbit IL 1ra immunoaffinity column , indicating that IL 1ra was responsible for this in vitro IL 1 inhibitory activity . pulmonary tissue levels of IL 1 beta pecked at 24 h ( 52 . 0 / 9 . 5 pg / mg ) after CFA injection , whereas IL 1ra levels peaked at 4 weeks ( …

Expression of a single chain human interleukin 12 gene in transgenic tobacco plants and functional studies. (2004 Mar)
expression of a single chain human interleukin 12 gene in transgenic tobacco plants and functional studies . interleukin 12 ( IL 12 ) is a key heterodimeric cytokine produced by a variety of antigen presenting cells , including dendritic cells , macrophages , and B cells . It displays a potent array of biological activities affecting natural killer ( NK ) and T cells . these activities include promotion of cell mediated or type 1 T helper cell responses ( Th1 ) . Due to that property , IL 12 has been employed in cancer immunotherapy , in mouse models of infectious diseases and in airway inflammation , and it may also have utility as a vaccine adjuvant . transgenic plants are being used in many laboratories around the world for the production of therapeutically valuable proteins and as vehicles for oral vaccines . Here we present the expression of a single chain human interleukin 12 in transgenic tobacco plants . The biological activity of plant produced IL 12 was determined by interferon gamma ( IFN gamma ) production by natural killer ( NK ) cells , and the level of production was comparable to that obtained with commercially available recombinant IL 12 . The potential use of this recombinant protein is discussed .

Interleukin 12 and antigen independently induce substance P receptor expression in T cells in murine schistosomiasis mansoni. (2001 Apr)
interleukin 12 and antigen independently induce substance P receptor expression in T cells in murine schistosomiasis mansoni . substance P ( SP ) regulates interferon gamma ( IFN gamma ) production through interaction with the SP receptor NK1 ( SPr ) on T cells at sites of inflammation . using murine schistosomiasis , we evaluated whether SPr expression was subject to immunoregulation . splenocytes from schistosome infected mice cultured for or 18 h did not express SPr , as determined by quantitative polymerase chain reaction assay . however , exposure to schistosome egg antigen ( SEA ) for or 4 h induced strong receptor expression . experiments using splenocytes fractionated with antibody coupled , paramagnetic beads showed that induction localized exclusively to T cells . receptor protein expression was confirmed with western blot . interleukin 12 ( IL 12 ) also induced strong T cell SPr expression . Both SEA and IL 12 remained strong inducers of T cell SPr in lymphocytes from the IL 12 ( p40 ) and IFN gamma R double knockout mouse , which suggested that SEA did not require IL 12 to induce SPr and that both worked independently of IFN gamma . splenocytes from wild type mice cultured with SEA and neutralizing anti IL 12 monoclonal antibody ( mAb ) also showed SPr induction . however , anti Ia mAb inhibited SEA induction of SPR : Thus , SPr is inducible on T cells . SEA induces SPr through interaction with T cell receptor …

Structure of a CXC chemokine receptor fragment in complex with interleukin 8. (1999 Mar)
structure of a CXC chemokine receptor fragment in complex with interleukin 8 . background : interactions between CXC chemokines ( e . g . interleukin 8 , IL 8 ) and their receptors ( e . g . CXCR 1 ) have a key role in host defense and disease by attracting and upregulating neutrophils to sites of inflammation . The transmembrane nature of the receptor impedes structure based understanding of ligand interactions . linear peptides based on the N terminal , extracellular portion of the receptor CXCR 1 do bind to IL 8 , however , and inhibit the binding of IL 8 to the full length receptor . results : The NMR solution structure of the complex formed between IL 8 and one such receptor based peptide indicates that a cleft between a loop and a beta hairpin constitute part of the receptor interaction surface on IL 8 . Nine residues from the C terminus of the receptor peptide ( corresponding to pro21 pro29 of CXCR 1 ) occupy the cleft in an extended fashion . intermolecular contacts are mostly hydrophobic and sidechain mediated . conclusions : The results offer the first details at an atomic level of the interaction between a chemokine and its receptor . consideration of other biochemical data allow extrapolation to a model for the interaction of IL 8 with the full length receptor . In this model , the heparin binding residues of IL 8 are exposed , thereby allowing presentation of the …

Involvement of p38 mitogen activated protein kinase in the induction of interleukin 12 p40 production in mouse macrophages by berberine … (2002 May)
involvement of p38 mitogen activated protein kinase in the induction of interleukin 12 p40 production in mouse macrophages by berberine , a benzodioxoloquinolizine alkaloid . interleukin ( IL ) 12 plays a pivotal role in the development of T helper type 1 ( Th1 ) immune response , which may have therapeutic effects on diseases associated with pathologic Th2 responses such as allergic disorders and asthma . In this study , we investigated the effects of berberine , a benzodioxoloquinolizine alkaloid with anti microbial and anti tumor activities , on the production of IL 12 p40 , an inducible subunit of IL 12 , in mouse macrophages . berberine induced IL 12 p40 production and activation of p38 mitogen activated protein kinase ( MAPK ) in dose dependent manners , which were significantly inhibited by p38 MAPK inhibitors and yohimbine , indicating that p38 MAPK and alpha ( 2 ) adrenergic receptor were involved in the induction of IL 12 p40 production in mouse macrophages by berberine . furthermore , berberine significantly enhanced IL 12 p40 production in mouse macrophages when combined with lipopolysaccharide , a well known inducer of IL 12 production . these findings may explain some of the known biological effects of berberine and suggests berberine as an immunotherapeutic compound for induction of IL 12 , which is potentially applicable for tumors , infectious disease , and airway inflammation .

Immunoregulatory effects of a synthetic monosaccharide. (1996 Mar)
immunoregulatory effects of a synthetic monosaccharide . investigative attempts to identify novel therapy for inflammatory connective tissue diseases continue to evolve . amiprilose hydrochloride ( amiprilose HCl ) is a synthetic carbohydrate shown to have anti inflammatory effects in animal models of inflammatory arthritis and in a multicenter clinical trial . interleukin 1 ( IL 1 ) is an important mediator of immune regulation , inflammation and joint destruction in arthritis . In the present study , the effects of amiprilose HCl on IL 1 activity , production and receptor distribution were investigated . Drug effects on IL 2 production and receptor distribution on lymphocytes were also explored . potential regulation of IL 1 activity was determined by monitoring the effects of amiprilose HCl on IL 1 stimulated proliferation of murine thymocytes and human synovial cells . inhibitory effects on IL 1 beta and IL 2 production by stimulated human peripheral blood monocytes were measured by elisa and lymphocyte IL 1 beta and IL 2 receptor distribution were analyzed by flow cytometry . The results from in vitro studies demonstrated that low concentrations of amiprilose HCl ( 1 100 micrograms / ml ) stimulated thymocyte proliferation and enhanced the proliferative response of IL 1 stimulated human synovial fibroblasts . IL 1 beta production in cultures of human peripheral blood monocytes was significantly decreased after exposure of the cultures to varying doses of amiprilose HCl as determined by elisa . exposure of mitogen activated human peripheral blood lymphocytes to amiprilose HCl …

Dynamic changes in mRNA expression of neutrophils during the course of acute inflammation in rabbits. (1994 May)
dynamic changes in mRNA expression of neutrophils during the course of acute inflammation in rabbits . To examine RNA / protein synthesis of neutrophils and related dynamic changes during the inflammatory process , we investigated mRNA expressions in neutrophils , by RNA blot hybridization analyses using 12 different rabbit gene probes . We first selected five candidate genes encoding inflammation related proteins , i . e . tumor necrosis factor ( TNF alpha ) IL 1 alpha , IL 1 beta , neutrophil activating peptide 1 / IL 8 ( NAP 1 / IL 8 ) and monocyte chemoattractant protein ( MCP ) 1 . We further selected several genes on basis of the results from gene subtraction between cDNA libraries from neutrophils at an early ( 5 h ) and at a late ( 24 h ) stage of casein induced acute peritonitis in rabbits , i . e . immune activation gene 2 ( Act 2 ) , migration inhibitory factor related protein 8 ( MRP 8 ) , MRP 14 , gamma actin , and formyl methionyl leucyl phenylalanine receptor ( fMLP R ) , and ferritin light ( L ) chain . In addition to these genes we used ferritin heavy ( H ) chain gene , another component of the ferritin molecule . We examined mRNA expressions by cytoplasmic slot blot analysis of the above 12 genes in neutrophils obtained from blood and from various stages of casein induced inflammation in rabbits . The observed …

Differential induction of interleukin I beta mRNA in the brain parenchyma of lewis and fischer rats after peripheral injection of … (2003 Jul)
differential induction of interleukin I beta mRNA in the brain parenchyma of lewis and fischer rats after peripheral injection of lipopolysaccharides . The expression of interleukin 1 beta ( IL 1beta ) mRNA was compared in the brain of inflammatory susceptible LEW / N and resistant F344 / N rats at 3 , 6 , and 12 h after peripheral administration of lipopolysaccharide ( LPS ) or saline . No differences between strains were observed in the circumventricular organs ( CVOs ) and choroid plexus . At 12 h after LPS administration , increased IL 1beta mRNA expression was detected in the hypothalamus of LEW / N rats . In contrast , increased IL 1beta mRNA expression was detected in the cerebral cortex of F344 / N rats . these data show region specific differences of IL 1beta mRNA expression in the brain of these rat strains that differ in their susceptibility to inflammation .

The interleukin 1 system : receptors , ligands , and ICE in the brain and their involvement in the fever … (1998 Jul)
The interleukin 1 system : receptors , ligands , and ICE in the brain and their involvement in the fever response . The ligands and the receptors of the interleukin 1 ( IL 1 ) system constitute a highly inducible set of proteins whose expression in infection and inflammation is of key importance in the host defense . The IL 1 system participates in the stimulation of the immune system , the neuroendocrine system , and the neuroimmune system . The major soluble and secreted agonist of the system , IL 1 beta , has been studied by mutational and transgenic approaches . furthermore , involvement of the signal transducing type I IL 1 receptor ( IL 1RI ) , in fever and other responses , has been studied by null mutation technique . We describe the inducible expression of the two agonists , IL 1 alpha ( 31 kDa and 17 kDa ) and IL 1 beta ( 17 kDa ) and of the IL 1 receptor subtypes IL 1RI and IL 1RII in the brain and in the adrenals ( as well as in the pituitary cell line att20 ) . We also describe an additional member of the IL 1 family : the IL 1 receptor antagonist ( IL 1ra ) , an endogenous antagonist to IL 1 alpha and IL 1 beta . furthermore , the IL 1 beta converting enzyme ( ICE ) and its differential regulation and expression in brain and adrenals is also …

Post translational regulation of interleukin 1 beta secretion. (1993 Aug)
Post translational regulation of interleukin 1 beta secretion . In view of the key role played by interleukin 1 ( IL 1 ) beta in inflammation , its production is likely to be precisely regulated . previous studies have shown that IL 1 beta biosynthesis is controlled at the transcriptional and translational levels . We have investigated whether post translational events also play a role in regulating the production of bioactive IL 1 beta . IL 1 beta , which lacks a signal sequence , is released by activated monocytes through a novel pathway of secretion , alternative to the classical endoplasmic reticulum golgi route . secretion of mature 17 kDA IL 1 beta is increased when pulse labelled activated monocytes are chased in the presence of heat aggregated immunoglobulins or of various drugs . febrile temperatures inhibit secretion of mature IL 1 beta , but only reduce its synthesis : treatment with cycloheximide restores secretion . processing of the 33 kDa precursor to the 17 kDa mature molecule is inhibited when the external pH is 8 or higher : under these conditions , release of unprocessed , biologically inactive 33 kDa IL 1 beta is observed . Thus , secretion of IL 1 beta is regulated by post translational mechanisms which operate at the level of both proteolytic processing and extracellular export .

The human interleukin 1 alpha gene is located on the long arm of chromosome 2 at band q13. (1989 Feb)
The human interleukin 1 alpha gene is located on the long arm of chromosome 2 at band q13 . interleukin 1 alpha ( IL 1 alpha ) and interleukin 1 beta ( IL 1 beta ) are two biochemically distinct , but distantly related , polypeptidic cytokines that play a key role in inflammation , immunologic reactions , and tissue repair . recently , it has been shown that IL 1 alpha is identical to hematopoietin 1 , which was described as a hematopoietic growth factor acting on early progenitor cells in synergy with other hematopoietic growth factors . In this report we discuss our use of in situ hybridization on human prometaphase cells with a human IL 1 alpha cDNA probe to localize the human IL 1 alpha gene on the proximal part of the long arm of chromosome 2 at band q13 , in the same chromosomal region as the IL 1 beta gene .

Interleukin 1 cluster combined genotype and restenosis after balloon angioplasty. (2003 Sep)
interleukin 1 cluster combined genotype and restenosis after balloon angioplasty . The interleukin 1 system is fundamentally involved in the pathogenesis of restenosis after percutaneous transluminal angioplasty ( PTA ) . In order to further define the clinical impact of genetic variation in this potent proinflammatory pathway we investigated the joint effects of two single nucleotide polymorphisms in the interleukin 1 beta gene IL 1B ( 511 ) and IL 1B ( 3954 ) and a variable number tandem repeat polymorphism in intron 2 of the interleukin 1 receptor antagonist gene ( IL 1RN VNTR ) on postintervention inflammation and occurrence of restenosis in 183 consecutive patients who underwent successful femoropopliteal PTA . C reactive protein ( CRP ) and serum amyloid A ( SAA ) were determined pre and 48 hours postintervention . patients were followed up to 12 months for the occurrence of postangioplasty restenosis ( or 50 ) . When analyzed separately , none of the polymorphisms was associated either with inflammation or restenosis . however , when the IL 1B ( 511 ) and the IL 1RN VNTR genotypes were combined , a highly significant relationship was observed : Non carriers of the two repeat allele of the IL 1RN VNTR ( IL 1RN 2 ) who were heterozygous and homozygous for the IL 1B ( 511 ) T allele exhibited a gradually increased inflammatory response and a higher restenosis risk . In contrast , carriers of the IL 1RN 2 and the IL 1B ( …

Stimulation of glycosaminoglycan synthesis in cultured human dermal fibroblasts by interleukin 1. (1989 Mar)
stimulation of glycosaminoglycan synthesis in cultured human dermal fibroblasts by interleukin 1 . induction of hyaluronic acid synthesis by natural and recombinant interleukin 1s and synthetic interleukin 1 beta peptide 163 171 . hyaluronic acid ( HA ) is believed to play a critical role in wound healing and in morphogenesis . factors controlling the production of HA by fibroblasts in normal and pathological states are not completely understood . In this report we have observed that natural human interleukin ( IL 1 ) 1 beta and human recombinant ( hrIL ) 1 alpha and beta are potent stimulators of HA production by fibroblasts in vitro . hyaluronic acid is the major species of glycosaminoglycan ( GAG ) stimulated by IL 1 in fibroblasts . PGE2 does not appear to be involved directly in this IL 1 effect on fibroblasts , but stimulation of HA production by IL 1 is dependent on protein synthesis . The synthetic human IL 1 beta peptide 163 171 ( Val Gln Gly Glu Glu Ser Asn Asp Lys ) , which has been previously shown to stimulate thymocyte proliferation but not fibroblast PGE2 production , is also able to stimulate fibroblast HA production . The synthesis and secretion of IL 1 by mononuclear phagocytes at sites of inflammation and immune reactions in vivo could potentially serve as a signal for fibroblasts to synthesize HA , which in turn could serve to facilitate and modulate reparative and immune processes by virtue of its ability to …

Local upregulation of corticotropin releasing hormone and interleukin 1 receptors in rats with painful hindlimb inflammation. (1997 Feb)
local upregulation of corticotropin releasing hormone and interleukin 1 receptors in rats with painful hindlimb inflammation . opioid peptides derived from immune cells produce analgesia by activating opioid receptors on peripheral sensory nerves in inflammation . corticotropin releasing hormone ( CRH ) and interleukin 1 beta ( IL 1 beta ) can release these opioids . Here we show that both corticotropin releasing hormone and interleukin 1 beta elicit receptor specific antinociception in inflamed paws of rats by an opioid mediated mechanism . autoradiographic studies demonstrate 125I CRH and 125I IL 1 beta binding sites on immune cells in lymph nodes and inflamed paws . This binding is of high affinity and displaceable by the respective unlabeled agonist and antagonist ligands but not by opioid or adrenergic compounds . 125I CRH and 125I IL 1 beta binding sites are absent on nerves and in non inflamed subcutaneous tissue but their number is greatly enhanced in inflamed paws and lymph nodes . This upregulation of binding sites for the opioid releasing agents corticotropin releasing hormone and interleukin 1 beta likely represents part of the body s local response to combat inflammatory pain .

Autoregulation of interleukin 1 production. (1989 May)
autoregulation of interleukin 1 production . interleukin 1 ( IL 1 ) alpha and beta are distinct cytokines with a common receptor on target cells . Both have been implicated in immunity , inflammation and connective tissue metabolism . their production is stimulated by microbial products and also by other cytokines derived from accessory cells and lymphocytes . following reports that IL 1 can stimulate its own production , we have tested the effects of recombinant IL 1 on the synthesis and release of IL 1 alpha and beta by human blood mononuclear cells ( MNC ) . We confirmed that autoinduction occurs but report also the novel finding that this effect is very concentration dependent . At some concentrations within the range found in vivo , recombinant IL 1 not only failed to stimulate further IL 1 production but also inhibited the background level of synthesis in 20 h MNC cultures . The negative feedback appears unrelated to prostaglandin E2 and interferon gamma levels and could not be reproduced by adding transforming growth factor beta . This previously unrecognized autoregulation may be relevant to clinical diseases associated with pathogenic over production of IL 1 .

Interleukin 18 is a potent proliferative factor for intestinal mucosal lymphocytes in crohn s disease. (2000 Dec)
interleukin 18 is a potent proliferative factor for intestinal mucosal lymphocytes in crohn s disease . background AIMS : crohn s disease ( CD ) is characterized by a marked accumulation of activated Th1 type CD4 ( ) T cells and macrophages in inflamed intestinal mucosa . interleukin ( IL ) 18 is a recently described cytokine that mainly exists in activated macrophages and shares biological activities with IL 12 in driving the development of Th1 type CD4 ( ) T cells by inducing interferon gamma . To clarify the role of IL 18 in intestinal inflammation in CD , we assessed the functional role of IL 18 in regulating intestinal mucosal lymphocytes . methods : serum IL 18 concentration was measured by enzyme linked immunosorbent assay . expression of IL 18 and IL 18 receptor in human intestinal mucosa was determined using immunohistochemistry and flow cytometry . The functional activity of IL 18 was assessed by the use of recombinant IL 18 to stimulate both the growth of intestinal mucosal lymphocytes and IL 2 receptor induction activity . results : The serum IL 18 concentration was significantly higher in patients with CD than normal controls . In the inflamed colonic mucosa of CD , many IL 18 ( ) CD68 ( ) macrophages had infiltrated the lamina propria . intestinal mucosal lymphocytes from CD expressed functional IL 18 receptors . recombinant IL 18 induced significant proliferative responses in freshly isolated mucosal lymphocytes from CD patients , but not from …