Inflammatory Bowel Disease Mucosa Research Articles

Controversies about the use of serological markers in diagnosis of inflammatory bowel disease

The serological markers are increasingly used in diagnosis of inflammatory bowel disease (IBD). D-lactate and diamine oxidase are new indicators that can be used to reveal the damage to intestinal mucosa and permeability alteration in IBD. Although the two biological markers seem more sensitive, recent clinical trials and animal experiments have shown controversies about the use of them in diagnosis of IBD. Therefore, these markers should be interpreted cautiously and further prospective studies are needed to establish their clinical role in diagnosis of IBD.

CD24 is upregulated in inflammatory bowel disease and stimulates cell motility and colony formation

We investigated whether CD24 (reportedly a stem cell marker and adhesion molecule) was expressed in regenerative mucosa in inflammatory bowel disease (IBD) and whether it could be functionally relevant. CD24 expression was examined in 10 cases of IBD and the relationship of CD24 with Wnt signaling was tested using dominant negative (DN)-TCF4 expression. For functional evaluation, CD24 was 1) cloned and forcibly expressed in HCT116 (which expresses very low levels of CD24) and 2) knocked-down by RNA interference in HT29 (which expresses high levels of CD24). The effect of altered CD24 expression on proliferation/apoptosis, staurosporine-induced apoptosis, colony formation in soft agar, migration, and invasion was examined. CD24 was not expressed in normal tissue, while 10/10 cases of IBD showed CD24 upregulation. Inhibition of Wnt signaling with DN-TCF4 caused CD24 downregulation. Forced expression of CD24 did not influence cell proliferation, apoptosis, or staurosporine-induced apoptosis but it did significantly enhance colony forming efficiency (P < 0.01). Furthermore, there was increased transwell migration (P < 0.001) and invasion (P < 0.03) and there was increased cell migration in wounding assays. Conversely, knockdown of CD24 reduced transwell migration (P < 0.01) and invasion (P < 0.01) and reduced cell motility in wounding assays. CD24 knockdown did not influence proliferation, apoptosis resistance, or staurosporine-induced apoptosis. This is the first study to report upregulation of CD24 in regenerating tissue in IBD. This may be regulated by Wnt signaling and can confer enhanced colony forming ability and enhanced cell motility-features that may be important in tissue healing in the colon.

Significant decrease of mucosal cytoglobin+ pericryptal myofibroblasts in longstanding ulcerative colitis with colorectal neoplasia, correlatively with alpha-SMA and HSP47 phenotypic expression

Cytoglobin (Cygb) is speculated to supply O2 to mitochondria and act as free radical scavenger to protect cells from oxidative stress. It also relates with organ fibrosis. We showed Cygb expression and characterization in hepatic stellate cells and splanchnic fibroblast-like cells1,2. Recently, we presented that colonic pericryptal (subepithelial) myofibroblasts and interstitial myofibroblasts correspond to colonic stellate cells3. Further, we have demonstrated that early genomic instability, including MSI and LOH, appeared not only in mucosal epithelial cells but also stromal cells in regenerative rectal mucosa of long-standing ulcerative colitis (UC) cases, suggesting the alteration of epithelial and mesenchymal interaction in UC-tumorigenesis4,5. Following the above described results, we tried to see Cygb expression and phenotypic alteration of pericryptal myofibroblasts and interstitial cells in the rectal mucosa in long-standing UC cases with or without colorectal neoplasia. Immunoreactive Cygb +, alpha-smooth muscle actin (alpha -SMA) +, heat shock protein (HSP)47+ pericryptal cells (/crypt) and interstitial cells (/lower half of mucosa propria, 250μm in length), respectively, were counted on frozen histologic sections of non-cancerous rectal mucosa of sporadic colorectal cancer (controls, 16; male 9, female 7; 64.6±14.6 y/o) and long-standing UC cases (total duration of illness >5 years) with (14; m 8, f 6; 53.1 ± 14.4 y/o) or without neoplasia (20; m 10, f 10; 46.8 ± 14.0 y/o), and results were compared each other. Cygb expression was demonstrated in pericryptal myofibroblasts and interstitial cells, similar to hepatic stellate cells by immunohistochemistry and immunoelectron microscopy. Coexpression of Cygb and alpha-SMA or HSP47 was also confirmed in some of pericryptal myofibroblasts and interstitial cells by double immunofluorescence method. Significant decrease of Cygb+ pericryptal myofibroblasts in long-standing UC cases without neoplasia was shown, correlatively with alpha-SMA+ or HSP47+ pericryptal cells, compared to controls. Further, Cygb+ pericryptal myofibroblasts were significantly decreased in long-standing UC cases with neoplasia, compared to without neoplasia, suggesting a suppressive role of Cygb in tumorigenesis. In contrast, Cygb+ or alpha-SMA + or HSP47+ interstitial cells increased in long-standing UC with and without neoplasia. Significant inverse correlations were also revealed between Cygb+ or alpha-SMA + or HSP47+ pericryptal myofibroblasts and interstitial cells, respectively, in relation with the progression of mucosal remodeling due to UC. Taken together, alterations of pericryptal myofibroblasts and interstitial cells may play an important role on colorectal tumorigenesis in UC.

Mucosal Gene Expression of Antimicrobial Peptides in Inflammatory Bowel Disease Before and After First Infliximab Treatment

BackgroundAntimicrobial peptides (AMPs) protect the host intestinal mucosa against microorganisms. Abnormal expression of defensins was shown in inflammatory bowel disease (IBD), but it is not clear whether this is a primary defect. We investigated the impact of anti-inflammatory therapy with infliximab on the mucosal gene expression of AMPs in IBD.Methodology/Principal FindingsMucosal gene expression of 81 AMPs was assessed in 61 IBD patients before and 4–6 weeks after their first infliximab infusion and in 12 control patients, using Affymetrix arrays. Quantitative real-time reverse-transcription PCR and immunohistochemistry were used to confirm microarray data. The dysregulation of many AMPs in colonic IBD in comparison with control colons was widely restored by infliximab therapy, and only DEFB1 expression remained significantly decreased after therapy in the colonic mucosa of IBD responders to infliximab. In ileal Crohn's disease (CD), expression of two neuropeptides with antimicrobial activity, PYY and CHGB, was significantly decreased before therapy compared to control ileums, and ileal PYY expression remained significantly decreased after therapy in CD responders. Expression of the downregulated AMPs before and after treatment (DEFB1 and PYY) correlated with villin 1 expression, a gut epithelial cell marker, indicating that the decrease is a consequence of epithelial damage.Conclusions/SignificanceOur study shows that the dysregulation of AMPs in IBD mucosa is the consequence of inflammation, but may be responsible for perpetuation of inflammation due to ineffective clearance of microorganisms.

Butyrate utilization by the colonic mucosa in inflammatory bowel diseases

The short-chain fatty acid butyrate, which is mainly produced in the lumen of the large intestine by the fermentation of dietary fibers, plays a major role in the physiology of the colonic mucosa. It is also the major energy source for the colonocyte. Numerous studies have reported that butyrate metabolism is impaired in intestinal inflamed mucosa of patients with inflammatory bowel disease (IBD). The data of butyrate oxidation in normal and inflamed colonic tissues depend on several factors, such as the methodology or the models used or the intensity of inflammation. The putative mechanisms involved in butyrate oxidation impairment may include a defect in beta oxidation, luminal compounds interfering with butyrate metabolism, changes in luminal butyrate concentrations or pH, and a defect in butyrate transport. Recent data show that butyrate deficiency results from the reduction of butyrate uptake by the inflamed mucosa through downregulation of the monocarboxylate transporter MCT1. The concomitant induction of the glucose transporter GLUT1 suggests that inflammation could induce a metabolic switch from butyrate to glucose oxidation. Butyrate transport deficiency is expected to have clinical consequences. Particularly, the reduction of the intracellular availability of butyrate in colonocytes may decrease its protective effects toward cancer in IBD patients.

CXCL12 Is a constitutive and inflammatory chemokine in the intestinal immune system

Inflammatory bowel disease (IBD) is characterized by increased lymphocytic infiltrate to the lamina propria (LP) and upregulation of inflammatory chemokines and receptors. CXCL12 is a constitutive chemokine involved in lung, brain, and joint inflammation. We hypothesized that CXCL12 and its receptor, CXCR4, would have a constitutive and inflammatory role in the gut. Intestinal epithelial cells (IECs) and T lymphocytes were isolated from intestinal mucosa of IBD and control patients undergoing bowel resection. Autologous T cells were isolated from peripheral blood (PB). CXCL12 and CXCR4 expression by IECs was assessed by polymerase chain reaction and immunohistochemistry, lymphocyte phenotype by flow cytometry, and migration by Transwells. IECs expressed CXCL12 and expression was increased and more diffuse in IBD compared to normal crypts (ulcerative colitis [UC] > Crohn's disease [CD], inflamed > noninflamed). CXCR4 was expressed by IECs, LP T cells (LPTs), and PB T cells (PBTs), and CXCR4+ cells were increased in IBD LP in situ. PBTs and LPTs from all patients had a high and comparable migration toward CXCL12 (P < 0.0001 and P < 0.05 vs. medium, respectively). Migration toward IBD-IEC-derived supernatant was significantly higher compared to normal. Antibodies against CXCR4 and CXCL12 blocked migration. CXCL12 is expressed by normal IECs and upregulated and differentially distributed in IBD IECs. CXCR4 is expressed by IECs and LPTs, and CXCR4+ cells are significantly increased in IBD LP. CXCL12 is chemotactic for both PBTs and LPTs. Thus, CXCL12 and CXCR4 have a constitutive and inflammatory role in the intestinal mucosa and their selective therapeutic manipulation may be considered in IBD management.

Differential regulation of interleukin 17 and interferon γ production in inflammatory bowel disease

Background and Aims:Interleukin 17 (IL17) is now known to be involved in a number of chronic inflammatory disorders. However, the mechanisms regulating its production in inflammatory bowel disease (IBD) are...

Increased serum levels of L-arginine in ulcerative colitis and correlation with disease severity

L-arginine (L-Arg) is a semi-essential amino acid that is the substrate for both nitric oxide and polyamine synthesis. Cellular uptake of L-Arg is an active transport process that is subject to competitive inhibition by L-ornithine (L-Orn) and L-lysine (L-Lys). We investigated L-Arg utilization in patients with ulcerative colitis (UC). Serum was collected from 14 normal controls and 22 UC patients with pancolitis of moderate or severe activity by histopathology score. The Mayo Disease Activity Index (DAI) and endoscopy subscore were assessed. Serum amino acid levels were measured by high-performance liquid chromatography. Arginine availability index (AAI) was defined as [L-Arg]/([L-Orn] + [L-Lys]). Serum L-Arg levels were significantly associated with histopathologic grade (P = 0.001). L-Arg levels were increased in subjects with severe colitis when compared to those with moderate colitis or normal mucosa. L-Orn + L-Lys levels were also increased in severe colitis, so that AAI was not significantly increased. L-Arg levels were also strongly associated with the endoscopy subscore (P < 0.001). There was a strong correlation between DAI and L-Arg levels (r = 0.656, P < 0.001). Serum L-Arg levels correlate with UC disease severity but availability is not increased due to competitive inhibition by L-Orn and L-Lys. Our findings suggest that L-Arg uptake by cells in the inflamed colon is defective, which may contribute to the pathogenesis of UC. Studies delineating the mechanism of uptake inhibition could enhance our understanding of UC or lead to novel treatment options.

Expression of IL-24, an Activator of the JAK1/STAT3/SOCS3 Cascade, Is Enhanced in Inflammatory Bowel Disease

IL-24 is a member of the IL-10 family of cytokines. In this study, we investigated IL-24 expression in the inflamed mucosa of patients with inflammatory bowel disease (IBD), and characterized the molecular mechanisms responsible for IL-24 expression in human colonic subepithelial myofibroblasts (SEMFs). IL-24 expression in the IBD mucosa was evaluated by immunohistochemical methods. IL-24 mRNA and protein expression was determined by real-time PCR and ELISA, respectively. AP-1 and C/EBP DNA-binding activity and IL-24 promoter activity were assessed by EMSA analysis and a reporter gene assay, respectively. IL-24 mRNA expression was significantly elevated in active lesions from patients who have ulcerative colitis and Crohn's disease. Colonic SEMFs were identified as a major source of IL-24 in the mucosa. IL-1beta, but not IL-17A, TNF-alpha, or IFN-gamma, significantly enhanced IL-24 mRNA and protein expression in isolated colonic SEMFs. The IL-1beta-induced IL-24 mRNA expression was mediated by the activation of the transcription factors, AP-1 and C/EBP-beta. Induction of IL-24 mRNA stabilization was also involved in the effects of IL-1beta. IL-24 induced JAK1/STAT-3 phosphorylation and SOCS3 expression in HT-29 colonic epithelial cells. IL-24 did not modulate the proliferation of HT-29 cells, but significantly increased the mRNA expression of membrane-bound mucins (MUC1, MUC3, and MUC4). IL-24 derived from colonic SEMFs acts on colonic epithelial cells to elicit JAK1/STAT-3 activation and the expression of SOCS3 and mucins, supporting their suppressive effects on mucosal inflammation in IBD.

860 Natural Killer T Cells Bearing IL-13rα2, Producing IL-13 and Having Cytotoxicity for Epithelial Cells Populate the Mucosa in Ulcerative Colitis

exposition in patients after pouch surgery (pouch patients versus IBD patients, p < 0.02). Conclusions:Increased cell shedding and transient epithelial cell destruction with subsequent bacterial translocation are newly discovered features of IBD pathophysiology. These changes can be identified and quantified in humans during ongoing colonoscopy using CLE. This might further support the notion that intrinsic micro-flora can trigger flares in patients with IBD. Thus, CLE might play a crucial role in the future for monitoring mucosal healing in patients with IBD. Epithelial changes of the terminal ileum before and after the exposition of rectal micro-flora

S1718 Expression of Interleukin-33, a Novel Member of the IL-1 Family, Is Increased in the Intestinal Mucosa and Serum of Ulcerative Colitis: A Potential Role of the IL-33/ST2 System in the Pathogenesis of IBD

S1718 Expression of Interleukin-33, a Novel Member of the IL-1 Family, Is Increased in the Intestinal Mucosa and Serum of Ulcerative Colitis: A Potential Role of the IL-33/ST2 System in the Pathogenesis of IBD

397 Notch1 Activation Promotes Goblet Cell Depletion and Expression of Pla2g2a in the Inflamed Mucosa of Ulcerative Colitis

397 Notch1 Activation Promotes Goblet Cell Depletion and Expression of Pla2g2a in the Inflamed Mucosa of Ulcerative Colitis

W1630 Oral Microbiota in Inflammatory Bowel Disease and Recurrent Aphthous Stomatitis

G A A b st ra ct s Our study suggest that impaired butyrate oxidation is closely linked to the sulphide detoxification capacity of the mucosa in ulcerative colitis. The sulphide detoxification mechanism could explain the well-documented observation that cigarette smoking is beneficial in UC. Smoking increases blood cyanide levels and the colon has been shown to extract cyanide from blood. Hence, this cyanide could enhance the removal of thiosulphate from the colonic mucosa and thus facilitate the metabolism of sulphide to thiosulphate.

In situ evidence of involvement of Schwann cells in ulcerative colitis: autocrine and paracrine signaling by A disintegrin and metalloprotease-17–mediated tumor necrosis factor α production

An increase in S100 protein-positive cells has been reported in inflammatory bowel diseases, mainly Crohn disease. These cells were interpreted as myeloid-derived dendritic cells, chiefly in follicular areas. We were prompted to assess the nature of these cells in interfollicular areas of inflamed colonic mucosa in ulcerative colitis and study their involvement in tumor necrosis factor alpha production, the main inflammatory cytokine in ulcerative colitis. The number and distribution of cells expressing S100 protein, nerve growth factor receptor, CD68, CD1a, CD83, and calretinin were studied in samples from 16 patients with active ulcerative colitis using simple and double immunohistochemistry. Then, the localization in S100 protein-positive cells of (1) tumor necrosis factor alpha, (2) its sheddase A disintegrin and metalloprotease-17, and (3) the receptors TNFR1 was assessed using double immunofluorescence followed by confocal microscopy. In active ulcerative colitis, there was an increased number in S100 protein-positive cells in interfollicular areas of colonic mucosa compared with quiescent ulcerative colitis, nonulcerative colitis, or normal mucosa. All S100 protein-positive cells ensheathed calretinin-positive axons, indicating their Schwann cell origin. No CD1a- or CD83-positive dendritic cells were detected. Double immunofluorescence studies showed that in normal colon, Schwann cells of the mucosa and submucosal plexuses weakly expressed A disintegrin and metalloprotease-17 but did not express tumor necrosis factor alpha. By contrast, in active ulcerative colitis, they expressed both A disintegrin and metalloprotease-17 and tumor necrosis factor alpha. Schwann cells as well as calretinin-positive axons strongly expressed TNFR1. This study shows (1) a Schwann cell proliferation in the inflamed colonic mucosa during active ulcerative colitis and (2) that Schwann cells produce tumor necrosis factor alpha. Tumor necrosis factor alpha is thus likely to stimulate Schwann cell proliferation through an autocrine/paracrine mechanism.

Il-21 enhances NK cell activation and cytolytic activity and induces Th17 cell differentiation in inflammatory bowel disease

Interleukin-21 (IL-21) is involved in T and NK cell activation and effector response and promotes Th17 cell differentiation. Here we investigated IL-21 receptor (IL-21R) expression in inflamed mucosa of inflammatory bowel disease (IBD) and evaluated its role in the induction of NK cell cytotoxicity and activation as well as Th17 differentiation. Expression of IL-21R was performed by immunohistochemistry and flow cytometry. NK cell cytotoxicity was detected by a standard (51)Cr-release assay. Cytokine levels were analyzed by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (PCR). IL-21R-positive cells were significantly increased in inflamed mucosa of IBD compared with controls, and mainly expressed in freshly isolated peripheral blood (PB)- and lamina propria (LP)-CD4(+), CD8(+) T, B, and NK cells. PB-NK cells from IBD patients produced higher levels of interferon gamma (IFN-gamma) and tumor necrosis factor (TNF) than controls when stimulated with immobilized human IgG and IL-21. IL-21-primed IBD NK cells showed a more potent antitumor cytotoxicity to NK-sensitive K562 cells than controls. Moreover, PB-T and LP-T cells from IBD patients produced large amounts of proinflammatory cytokines (e.g., TNF, IFN-gamma) than controls when stimulated with IL-21 and anti-CD3. Importantly, IL-21 facilitated IBD CD4(+) T cell to differentiate into Th17 cells, characterized by increased expression of IL-17A and ROR gamma t. IL-21 enhances IBD NK cell cytotoxic response, triggers T cells to produce proinflammatory cytokines, and induces IBD CD4(+) T cells to differentiate into Th17 cells, suggesting that IL-21 is involved in the pathogenesis of IBD and that blocking IL-21R signaling may have a therapeutic potential in IBD.

IL1β‐ and LPS‐induced serotonin secretion is increased in EC cells derived from Crohn’s disease

Gut mucosal enterochromaffin (EC) cells are regarded as key regulators of intestinal motility and fluid secretion via secretion of serotonin (5HT), are increased in numbers in mucosal inflammation and located in close proximity to immune cells. We examined whether interleukin (IL)1beta and Escherichia coli lipopolysaccharide (LPS) induced EC cell 5HT release through Toll-like/IL-1 (TIL) receptor activation, nuclear factor kappa B (NFkappaB) and mitogen-activated protein kinase (MAPK) phosphorylation and evaluated whether somatostatin could inhibit this phenomenon. Pure (>98%) human intestinal EC cells were isolated by fluorescent activated cell sorting from preparations of normal (n = 5) and Crohn's colitis (n = 6) mucosa. 5HT release was measured (ELISA), and NFkappaB and ERK phosphorylation quantitated (ELISA) in response to IL1beta and LPS. 5HT secretion was increased by both E. coli LPS (EC(50) = 5 ng mL(-1)) and IL1beta (EC(50) = 0.05 pmol L(-1)) >2-fold (P < 0.05) in Crohn's EC cells compared with normal EC cells. Secretion was reversible by the TLR4 antagonist, E. coli K12 LPS (IC(50) = 12 ng mL(-1)) and the IL1beta receptor antagonist (ILRA; IC(50) = 3.4 ng mL(-1)). IL1beta caused significant (P < 0.05) NFkappaB and MAPK phosphorylation (40-55%). The somatostatin analogue, lanreotide inhibited IL1beta-stimulated secretion in Crohn's (IC(50) = 0.61 nmol L(-1)) and normal EC cells (IC(50) = 1.8 nmol L(-1)). Interleukins (IL1beta) and bacterial products (E. coli LPS) stimulated 5HT secretion from Crohn's EC cells via TIL receptor activation (TLR4 and IL1beta). Immune-mediated alterations in EC cell secretion of 5HT may represent a component of the pathogenesis of abnormal bowel function in Crohn's disease. Inhibition of EC cell-mediated 5HT secretion may be an alternative therapeutic strategy in the amelioration of inflammatory bowel disease symptomatology.

DIFFERENTIAL REGULATION OF INTERLEUKIN-17 AND INTERFERON-GAMMA PRODUCTION IN INFLAMMATORY BOWEL DISEASE

BACKGROUND AND AIMS: Interleukin 17 (IL17) is now known to be involved in a number of chronic inflammatory disorders. However, the mechanisms regulating its production in inflammatory bowel disease (IBD) are still unclear. METHODS: Endoscopic biopsies or surgical specimens were taken from inflamed and uninflamed colonic mucosa of 72 patients with IBD (38 with Crohn's disease and 34 with ulcerative colitis), and normal colon of 38 control subjects. IL17 and interferon gamma (IFNgamma) were detected by ELISA in the supernatants of biopsies cultured ex vivo, and anti-CD3/CD28-stimulated lamina propria mononuclear cells (LPMCs) incubated with IL12, IL23, IL1beta plus IL6, transforming growth factor beta1 (TGFbeta1), or anti-IL21 neutralising antibody. Intracellular flow cytometry was performed to analyse mucosal Th17 and Th1/Th17 cells. RESULTS: IL17 production by organ culture biopsies was higher in IBD inflamed mucosa than IBD uninflamed mucosa and controls, and was equivalent in amount to IFNgamma. Anti-CD3/CD28-stimulated IBD LPMCs produced higher IL17 amounts compared to controls. The percentages of Th17 and Th1/Th17 cells were increased in patients with IBD. IL23 and IL1beta plus IL6 had no effect on IBD LPMC production of IL17; however, IL12 markedly increased IFNgamma production and decreased IL17 production. TGFbeta1 dose-dependently decreased IFNgamma, but had no significant inhibitory effect on IL17 production. Blocking IL21 significantly downregulated IL17 production. CONCLUSIONS: Our findings support a role for IL12, TGFbeta and IL21 in modulating IL17/IFNgamma production in IBD. The abundant IL17 in inflamed IBD mucosa may help explain the relative lack of efficacy of anti-IFNgamma antibodies in clinical trials of Crohn's disease.

Tipping the balance: modulating the Wnt pathway for tissue repair

The Wnt signaling pathway has a crucial role in regulating cell growth and differentiation and is required for tissue homeostasis and repair. Although constitutive activation of the Wnt pathway can lead to abnormal cell growth and cancer, modulation of Wnt signaling might have a therapeutic benefit for tissue regeneration in numerous diseases. Recently, preclinical studies have demonstrated that treatments with antibodies against the Wnt inhibitor Dickkopf1 (DKK1) and with the positive Wnt modulator R-Spondin1 (RSpo1) were sufficient to repair the bone lesions in multiple myeloma and rheumatoid arthritis and to restore the damaged mucosa in experimental colitis, respectively. A remarkable balance is set for Wnt signaling by secreted proteins such as RSpo1 and DKK1, which help to regulate tissue homeostasis. As physiological Wnt response is essential for the regeneration of damaged tissues, modulation of the Wnt pathway might be beneficial for the treatment of multiple human diseases.

Therapeutic leukocytapheresis in inflammatory bowel disease: clinical efficacy and mechanisms of action

Intense infiltration of the intestinal mucosa by activated leukocytes is a hallmark of inflammatory bowel disease (IBD). Therefore, removal of circulating leukocytes may be an attractive approach for treating IBD. Leukocytapheresis with Cellsorba, a column of polyethylenephtarate fibers that captures monocytes, granulocytes and lymphocytes, has been used to treat IBD, particularly ulcerative colitis, in Japan and Europe. This article reviews the clinical efficacy and safety data and the mechanisms of action of leukocytapheresis in IBD. Although the majority of clinical studies enrolled only small numbers of patients and had open-labeled designs, leukocytapheresis showed clinical efficacy with an excellent safety profile. Leukocytapheresis depletes granulocytes, monocytes, lymphocytes and platelets, alters cell population profiles, modulates cytokine production, and induces bone marrow-derived cells. In conclusion, leukocytapheresis exerts anti-inflammatory and tissue-repairing effects on the intestinal mucosa in IBD. Further studies are needed to explain the exact mechanism of action and to determine the true efficacy of this approach.

Growth factors as treatment for inflammatory bowel disease: A concise review of the evidence toward their potential clinical utility

In the process of inflammation and repair of the intestinal mucosa in inflammatory bowel disease (IBD), there occurs a complex and an unknown interplay of innate and adaptive immune mechanisms. This interaction of factors may explain why IBD is characterized by a relapsing and remitting clinical course. Different components of innate immunity, hormones and interleukins in IBD have been suggested to be impaired. The growth hormone, epidermal growth factor, keratinocyte growth factor and colony-stimulating factors have emerged as potential tools for the modulation of intestinal inflammation and repair. Despite promising results of initial studies, the evidence that justify treatment of patients in clinical practice is not enough as some of the trials are nonrandomized or included a small number of patients. In this concise review, we provide a summary of the most recent and relevant evidence regarding the potential therapeutic effects of growth factors in IBD.