vasoactive-intestinal-peptide and Colitis--Ulcerative

Ulcerative colitis (UC) is a chronic relapsed intestinal disease with an increasing incidence around the world. The pathophysiology of UC remains unclear. However, the role of the interaction between the enteric nervous system and the immune system in the pathogenesis of UC has been the focus of attention and has become a research hotspot. Vasoactive intestinal peptide (VIP) is a kind of endogenous neuropeptide with regulatory activity on intestinal immunity. It has been shown to regulate immune disorders in animal and human experiments and has become an effective anti-inflammatory and immune modulator that affects the innate immune system and adaptive immune system. Regulatory B cells (Bregs) are a new group of B cells that negatively regulate the immunity and have received extensive attention in immune circles. Bregs can regulate immune tolerance by producing interleukin (IL)-10, IL-35, and transforming growth factor-β, suppressing autoimmune diseases or excessive inflammatory responses. The secretion of IL-10 by Bregs induces the development of T helper (Th) 0 and Th2 cells. It also induces Th2 cytokines and inhibits Th1 cytokines, thereby inhibiting Th1 cells and the Th1/Th2 balance. With further clarity on the mechanism of the regulation of IL-10 expression by VIP in Bregs in colitis patients, we believe that Bregs can provide a novel strategy for the clinical treatment of UC. Thus, we aim to review the current literature on this evolving topic.

Topics: Animals; B-Lymphocytes, Regulatory; Colitis, Ulcerative; Humans; Interleukin-10; Th1 Cells; Vasoactive Intestinal Peptide

Small intestinal dysfunction has been described in patients with ulcerative colitis and in experimental animal models of colitis. This is demonstrated by a decrease in fluid, electrolyte, amino acid, fat and carbohydrate absorption as well as by deranged intestinal motility. Histopathological changes in the small intestines in colitis have not been consistently demonstrated, but there is evidence of structural and biochemical alterations as shown by increased intestinal permeability and a decrease in the expression of multiple brush border membrane enzymes such as disaccharidases and aminopetidases, in both humans and experimental animals. The pathophysiology of this dysfunction has not been elucidated, but it is thought to include alterations in neural circuitry such as increased neuronal excitability, neuronal damage and changes of neuropeptidergic innervation and receptors as well as an increase in local production of pro-inflammatory cytokines and alterations in the production of some neurohumoral mediators. In the following, we provide an update on the advancement of clinical and scientific contributions to elucidate the underlying mechanisms of the alteration of the functions of apparently intact small intestinal segments, induced by ulcerative colitis.

Topics: Animals; Colitis, Ulcerative; Cytokines; Enteric Nervous System; Gastrointestinal Motility; Humans; Intestine, Small; Malabsorption Syndromes; Nitric Oxide; Permeability; Serotonin; Vasoactive Intestinal Peptide

Inflammatory bowel diseases (IBD) are driven by imbalances in innate and acquired immune response. In IBD two dysregulated T cell subsets are in the focus of interest: activated effector T cells and regulatory T cells. These T cell subsets are characterized by a strong expression of the ectopeptidases dipeptidyl peptidase IV (DPIV /CD26) and aminopeptidase N (APN/CD13), which are thought to a role in the control of immune activation and in regulating cellular communication by hydrolyzing bioactive polypeptides. Since inhibitors of both enzymes were shown to be effective in limiting immune activation processes in vitro as well as in vivo, they emerged as new drug candidates for the treatment of diseases associated with an imbalanced T cell response, such as IBD. In this review we intent to throw light on the putative role of DPIV, APN and related enzymes in the regulation of immune and non-immune processes in inflammatory bowel diseases, on possible benefits from peptidase inhibitor therapy in these diseases as well on the gaps of knowledge in this field.

Topics: Brain; CD13 Antigens; Colitis, Ulcerative; Dipeptidyl-Peptidase IV Inhibitors; Gastrointestinal Tract; Humans; Inflammatory Bowel Diseases; Protease Inhibitors; Substance P; T-Lymphocyte Subsets; Vasoactive Intestinal Peptide

Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Asthma; Autoantibodies; Colitis, Ulcerative; Fibroblasts; Humans; Lentivirus Infections; Nasal Polyps; Pulmonary Disease, Chronic Obstructive; Th2 Cells; Vasoactive Intestinal Peptide; Viral Envelope Proteins; Virus Latency

Vasoactive intestinal polypeptide (VIP) is a 28 amino acid peptide which is localised in both the central and peripheral nervous system. In the human colon VIP is found in all layers and the highest concentrations have been found in the myenteric plexus. It is known that VIP has various effects on intestinal functions: i) it is a potent stimulant of mucosal water and electrolyte secretion; ii) it is involved in the peristaltic reflex; and iii) plays an inhibitory role on immune cell function. Based on these biological effects it has been hypothesized that the intestinal mucosal immune system and inflammation may be influenced by alterations in the tissue concentrations of VIP. Some authors have demonstrated no changes in the VIP colonic content of patients with ulcerative colitis, whereas others have demonstrated a reduction. Our results, using specific radioimmunoassay, showed that there is a significant decrease of VIP in both rectal and colonic mucosa of patients with ulcerative colitis as compared to controls. The VIP decrease is selective since substance P and calcitonin gene-related peptide were unchanged in the mucosal tissue of ulcerative colitis patients and furthermore the VIP alteration is correlated to the degree of mucosal inflammation. These findings suggest that the reduction of VIP mucosal content, even if it represents a non-specific event, could influence local inflammatory response and the activity of the disease.

Topics: Colitis, Ulcerative; Humans; Intestinal Mucosa; Rectum; Vasoactive Intestinal Peptide

Topics: Adrenal Cortex Hormones; Adult; Cell Membrane Permeability; Child; Colitis, Ulcerative; Crohn Disease; Diarrhea; Diet; Energy Intake; Gastrointestinal Motility; Humans; Intestinal Absorption; Intestinal Mucosa; Prostaglandins; Sulfasalazine; Vasoactive Intestinal Peptide; Water-Electrolyte Imbalance; Zinc

The links between stagnation of the Liver-Qi in the pathogenesis and ulcerative colitis (UC) were clinically and experimentally studied using the principle of nourishing the Liver in treated group and the principle of invigorating the Spleen in control group. The results showed that the effective rate was 96% in treated group and 82% in control group, and the difference was significant (P < 0.05); the formation rate of E rosettes and the transformation rate of lymphocytes were significantly raised in the two groups compared with the pre-treatment period, treated group was evidently superior to control group in the rate of dysfunction of autonomous nerve system (P < 0.01). The level of intestinal styrenated phenol (SP) and vasoactive intestinal polypeptide (VIP) of UC model were determined in rats. The results showed that the level of SP and VIP significantly increased in UC model group. They markedly lowered in treated group compared with model group (P < 0.01) and there was significant difference in comparing with control group (P < 0.01). It revealed that Wei Chang Ning, a drug to nourishing the Liver, had the action of regulating neurological -endocrinological (gastrointestinal hormone)-immunological system.

Topics: Adult; Animals; Colitis, Ulcerative; Colon; Drugs, Chinese Herbal; Female; Gastrointestinal Agents; Humans; Lymphocyte Activation; Male; Middle Aged; Rats; Rats, Wistar; Rosette Formation; Substance P; Vasoactive Intestinal Peptide

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) which is related to an immunological imbalance of the intestinal mucosa. Many clinical evidences indicate probiotics supplementation appears to be effective and safe in patients with UC. Vasoactive intestinal peptide (VIP) is an endogenous neuropeptide with multiple physiological and pathological effects. In this study, we investigated the protective effect of the combination of Lactobacillus casei ATCC 393 (L. casei ATCC 393) with VIP on dextran sodium sulfate (DSS)-induced UC in mice and the potential mechanism. The results showed that, compared with the control group, DSS treatment significantly shortened the colon length, caused inflammation and oxidative stress, and further resulted in the intestinal barrier dysfunction and gut microbiota dysbiosis. In addition, intervention with L. casei ATCC 393, VIP or L. casei ATCC 393 combined with VIP significantly reduced UC disease activity index. However, compared with L. casei ATCC 393 or VIP, L. casei ATCC 393 combined with VIP effectively relieved symptoms of UC by regulating immune response, enhancing antioxidant capacity, and regulating nuclear factor kappa-B (NF-κB) and nuclear factor erythroid-derived-2-like 2 (Nrf2) signaling pathways. In conclusion, this study suggests that L. casei ATCC 393 combined with VIP can effectively relieve DSS-induced UC, which is a promising treatment strategy for UC.

Topics: Animals; Colitis; Colitis, Ulcerative; Colon; Dextran Sulfate; Dextrans; Disease Models, Animal; Gastrointestinal Diseases; Lacticaseibacillus casei; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2; NF-kappa B; Signal Transduction; Vasoactive Intestinal Peptide

To evaluate the efficacy of vasoactive intestinal peptide (VIP) in treating ulcerative colitis (UC), targeting colonic mitochondrial dysfunction by virtue of its free radical scavenging properties for maintenance of colon mucosal integrity.. A murine model was administered with dextran sodium sulfate (DSS) to induce colitis in C57BL/6J mice at 3.5%/g bodyweight for 3 cycles of 5 days each, followed by an intraperitoneal dose of VIP at 0.5 nmol/L per mouse per day for 10 days. The post-treatment mice were sacrificed and their colon samples were utilized for further analysis. To substantiate the in vivo findings and identify the reactive species involved in progression of UC, Caco-2 cells were subjected to DSS (5%) for 24 hours at 37 °C with or without VIP (10 nmol/L) in the presence or absence of specific free radical scavengers and antioxidants.. Treatment with VIP reduced histopathological severity of colitis and cell death markers in murine model, leading to partial recovery of inhibited mitochondrial respiratory complexes, altered mitochondrial membrane potential and lowered adenosine triphosphate generation. Interestingly, in vitro treatment with VIP restored mitochondrial functions and its efficacy was equal to super oxide dismutase and dimethyl sulfoxide, indicating involvement of superoxide free radical (O. By virtue of its free radical scavenging properties VIP can act as a potent anti-colitogenic agent, reversing colonic mitochondrial dysfunction for treating UC.

Topics: Animals; Caco-2 Cells; Colitis; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Humans; Intestinal Mucosa; Mice; Mice, Inbred C57BL; Mitochondria; Vasoactive Intestinal Peptide

Mast cells (MCs) and vasoactive intestinal polypeptide (VIP) have been proposed as regulators of the intestinal barrier and inflammation. Our aim was to map the distribution in inflammatory bowel disease (IBD) and murine colitis.. MCs, VIP, and VIP-receptors (VPACs) were quantified by immunofluorescence and enzyme-immunoassay (EIA) in ileal tissues (villus epithelium (VE) and adjacent VE, ie, VE next to the follicle-associated epithelium, (FAE)) from Crohn's disease (CD; n = 16) and non-IBD patients, and in colonic specimens of ulcerative colitis (UC; n = 12) and healthy controls (HCs). In addition, VIP levels were measured in plasma from HCs, non-IBD, and IBD in remission (CD n = 30; UC n = 30). Colon, ileum, and plasma from mice with dextran sulfate sodium (DSS)-induced colitis and control mice were analyzed likewise.. FAE-adjacent VE in ileum of CD possessed more MCs (P < 0.05) and MCs expressing VPAC1 (P < 0.05), but not VPAC2, compared to controls. Both adjacent and regular VE of CD had more MCs co-localizing/in close proximity to VIP (P < 0.05). In UC colon, more MCs (P < 0.0005), MCs close to VIP (P < 0.0005), and MCs expressing VPAC1 (P < 0.05) were found compared to controls. VIP levels were elevated in plasma from CD and UC compared to controls (P < 0.0005). Colon of DSS mice showed more MCs and MCs close to VIP (P < 0.05) compared to control mice. In vitro experiments revealed MCs expressing VPACs and internalized VIP after 120 minutes of VIP-stimulation.. Communication between MCs and VIP is upregulated during IBD and mice colitis. In CD patients, the epithelium next to FAE seems to be more involved than the surrounding VE, suggesting increased MC-VIP-interactions in this intestinal region.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Cell Count; Colitis, Ulcerative; Crohn Disease; Dextran Sulfate; Female; Humans; Ileum; Inflammatory Bowel Diseases; Intestinal Mucosa; Male; Mast Cells; Mice, Inbred BALB C; Middle Aged; Receptors, Vasoactive Intestinal Polypeptide, Type I; Up-Regulation; Vasoactive Intestinal Peptide; Young Adult

Inflammatory bowel disease (IBD) is a chronic relapsing disorder of the intestine, with increasing incidence worldwide. At present, the management of IBD is an unmet medical need due to the ineffectiveness of currently available drugs in treating all patients, and there is strong demand for novel therapeutics. In this regard, vasoactive intestinal peptide, a potent anti-inflammatory endogenous hormone, has shown promise in managing multiple immune disorders in animal models. However, when administered in the free form, VIP undergoes rapid degradation in vivo, and with continuous infusion, it causes severe dose limiting side effects. To overcome these barriers, we have developed a superior mode to deliver VIP in its native form, using sterically stabilized micelles (VIP-SSM). Our previous studies demonstrated that, VIP, when administered in SSM, prevented joint damage and inflammation in a mouse model of rheumatoid arthritis at a significantly lower dose than the free peptide, completely abrogating the serious side effect of hypotension associated with VIP. In the current study, we demonstrate the therapeutic benefit of VIP-SSM over free peptide in reversing severe colitis associated with IBD. First, we conducted preliminary studies with dextran sulfate sodium (DSS) induced colitis in mice, to determine the effectiveness of VIP administered on alternate days in reducing disease severity. Thereafter, a single intra peritoneal injection of VIP-SSM or the free peptide was used to determine its therapeutic effect on the reversal of colitis and associated diarrhea. The results demonstrated that when administered on alternate days, both VIP-SSM and VIP were capable of alleviating DSS colitis in mice. However, when administered as a single dose, in a therapeutic setting, VIP-SSM showed superior benefits compared to the free peptide in ameliorating colitis phenotype. Namely, the loss of solid fecal pellets and increased fluid accumulation in colon resulting from DSS insult was abrogated in VIP-SSM treated mice and not with free VIP. Furthermore, reduced protein and mRNA levels of the major chloride bicarbonate exchanger, down regulated in adenoma (DRA), seen with DSS was reversed with VIP-SSM, but not with the free peptide. Similarly, VIP-SSM treatment significantly reduced the elevated mRNA levels of pro-inflammatory cytokines and showed significant histologic recovery when compared to mice treated with free VIP. Therefore, these results demonstrated that as a si

Topics: Animals; Colitis; Colitis, Ulcerative; Dextran Sulfate; Humans; Inflammatory Bowel Diseases; Mice; Micelles; Nanomedicine; Vasoactive Intestinal Peptide

To observe effects of treatment from the lung and treatment from the intestine on the level of vasoactive intestinal peptide (VIP) in the lung and intestine of ulcerative colitis (UC) rats.. The UC rat model was established in 52 rats by using rabbit intestine mucosa tissue allergen combined TNBS-ethanol model (with the model successful rate of 78.0%). Eight rats randomly selected from 40 successfully modeled rats and 8 of 16 rats from the normal group were recruited as the model group and the normal control group before intervention (at week 0). The rest 32 successfully modeled rats were randomly divided into the model group, the Western medicine treatment group (salazosulfapyridine), the treatment from lung group (Huangqi Jiegeng Decoction), and the treatment from intestine group (Huangqi Huanglian Decoction), 8 in each group. Rats in each treatment group were administered with corresponding medication 8 times the dose of a 60 kg adult human. Another 8 normal rats were recruited as the normal group. Equal volume of pure water was given to rats in the model group and the normal group by gastrog avage, once per day. Contents of VIP in the lung tissue and the intestinal tissue were detected at week 0 and 4 after 4-week consecutive intervention. Pathomorphological changes of the lung tissue and the colon tissue were observed under light microscope.. Compared with the normal control group at week 0, evenly distributed diffuse inflammation could be seen in the pulmonary interstitial tissue; the bronchial wall was thickened; a huge amount of infiltration surrounded bronchi and blood vessels; a large area of necrosis of intestinal mucosa and inflammatory cell infiltration could also be seen in the model group. Pathological injuries of the lung and the colon were more alleviated in each treatment group than in the model group at the same time point. Compared with the normal control group at the same time point, VIP contents in the lung tissue significantly decreased in the model group at the end of week 4 (P<0.05); VIP contents in the colon tissue significantly increased in the model group at the end of week 0 and 4 (P <0.05). Compared with the model group, VIP contents in the lung tissue significantly increased in the Western medicine treatment group and the treatment from lung group at the end of week 4 (P<0.01); VIP contents in the colon tissue significantly decreased in the treatment from lung group and the treatment from intestine group (P<0.05, P<0.01).. Treatment from the lung and treatment from the intestine showed predominant advantage in improving local inflammation of the lung and the intestinal tract, alleviating pathological injuries, promoting repair of injuries through regulating VIP contents in the lung tissue and the colon tissue.

Topics: Animals; Colitis, Ulcerative; Drugs, Chinese Herbal; Intestinal Mucosa; Intestines; Lung; Male; Rabbits; Rats; Vasoactive Intestinal Peptide

To discuss the feasibility of the pharmacodynamic evaluation method for traditional Chinese medicine (TCM) formula particles, with traditional decoction for reference and the intervention of Magnoliae Officinalis Cortex in rats with ulcerative colitis (UC). First of all, the similarity of traditional Magnoliae Officinalis Cortex decoction and formula particles of different manufacturers was defined by using the IR fingerprint. The UC rat model was established and given Houpo formula particles of different doses and manufacturers, with the decoction for reference, in order to observe disease activity index (DAI), colon mucosa damage index (CMDI), pathologic changes, nitric oxide (NO), endothdin (ET), substance P, vasoactive intestinal peptide (VIP). Their intervention effects on UC rats were compared to study the difference between Sanjiu and Tianjiang Houpo formula particles, in order to demonstrate the feasibility of the pharmacodynamic evaluation method for Houpo formula particles. According to the results, Houpo formula particles showed similar pharmacodynamic actions with the traditional decoction. The pharmacodynamic comparison of Houpo formula particles of different manufacturers showed no statistical significance. The experiment showed that on the basis of the TCM compounds, a prescription dismantlement study was conducted to define target points of various drugs. The traditional decoction was selected for reference in the comparison of corresponding formula particles for their pharmacodynamic equivalence. This method could avoid controversies about single or combined boiling of formula particles, and give objective comments on the pharmacodynamic effect of the formula particles. The method is proved to be feasible.

Topics: Animals; Chemistry, Pharmaceutical; Colitis, Ulcerative; Dosage Forms; Drug Evaluation, Preclinical; Drugs, Chinese Herbal; Humans; Magnolia; Male; Rats; Rats, Wistar; Substance P; Vasoactive Intestinal Peptide

Vasoactive intestinal peptide (VIP) has a number of important effects in intestinal physiology and pathology, including in ulcerative colitis (UC). The expression patterns of the predominant VIP receptor in the mucosa (the VPAC1 receptor) are unknown for the mucosa in UC. It is assumed that the sources of VIP in the intestine are the innervation and the inflammatory cells.. The VIP and VPAC1 receptor expression patterns in the epithelial layer of UC and non-UC patients were examined in the present study. The influence of marked inflammation of the mucosa was evaluated.. Specimens of the human colon, including the colon of UC patients, were examined concerning expressions of VIP and VPAC1 receptor, focusing on the epithelial layer. Immunohistochemistry and in situ hybridization were utilized.. There were VIP mRNA reactions and also marked VPAC1 receptor immunoreactions in the normal and slightly/moderately affected epithelium. VIP mRNA reactions were not detected and VPAC1 immunoreactions were minimal in response to marked mucosal derangement.. The findings suggest that there is a local production of VIP in the epithelial cells in normal and slightly/moderately inflamed mucosa but not in severely inflamed mucosa. Furthermore, a marked downregulation in VPAC1 receptor expressions occurs in the epithelium in severe UC. Based on the knowledge that VIP can have trophic, healing and anti-inflammatory effects, it is likely that the decrease in VIP mRNA and VPAC1 receptor reactions seen in severely affected mucosa in UC may be associated with adverse effects on intestinal function.

Topics: Adult; Colitis, Ulcerative; Down-Regulation; Female; Humans; Immunohistochemistry; In Situ Hybridization; Intestinal Mucosa; Male; Middle Aged; Receptors, Vasoactive Intestinal Polypeptide, Type I; Vasoactive Intestinal Peptide

Immunoglobulin-positive lymphocytes are present close to vasoactive intestinal polypeptide-positive (VIP(+)) nerve fibers in the lamina propria of the intestinal tract, and have an important role in mucosal defense. The number of immunoglobulin A-positive (IgA(+)) cells close to the epithelial basement membrane and nerve fibers is increased by the administration of lipopolysaccharides, which induce IgA secretion into the intestinal lumen. The relationship between immunoglobulin-positive lymphocytes and the VIP(+) nerve fibers during inflammation, such as in inflammatory bowel disease, however, is not well known. The morphological relationship between immunoglobulin-positive cells and the basement membrane or the VIP(+) nerve fibers in the colon was examined using double immunofluorescent labeling in an inflammatory bowel disease mouse model created by oral administration of dextran sodium sulfate (DSS). DSS administration induced goblet cell loss, crypt loss, intestinal epithelium deformation and infiltration of inflammatory cells in the mucosa. In the colon, the number and percentage of IgA(+) lymphocytes close to the basement membrane and the VIP(+) nerve fibers in the lamina propria increased after DSS administration, in parallel with the pathologic progress in the inflamed tissue. On the other hand, the percentage of immunoglobulin G-positive (IgG(+)) lymphocytes close to the basement membrane and the VIP(+) nerve fibers decreased, although the total number of IgG(+) lymphocytes in the lamina propria increased. We suggest that the immunoglobulin-producing lymphocytes and enteric nerve fibers in the colon normally have a close morphological relationship, and that this relationship is reinforced in a cell-specific manner during inflammation.

Topics: Animals; Chemotaxis, Leukocyte; Colitis, Ulcerative; Dextran Sulfate; Disease Models, Animal; Enteric Nervous System; Fluorescent Antibody Technique; Immunity, Mucosal; Immunoglobulin A; Lymphocytes; Male; Mice; Mice, Inbred ICR; Microscopy, Confocal; Nerve Fibers; Vasoactive Intestinal Peptide

To investigate the role of mast cells and gut hormones and their interactions in TNBS-induced ulcerative colitis.. Rat models of ulcerative colitis were established by a single intracolonic injection of 100 mg/kg TNBS (in 0.3 ml 50% ethanol). At 0, 6, 11, 16, 21 days after TNBS injection, the rats were sacrificed to determine the count of the mast cells. Histamine level in the whole blood, and the levels of histamine, substance P (SP), vasoactive intestinal peptide (VIP), and somatostatin (SS) in the distal colons were measured by fluorimetry or radioimmune assay. Immunofluorescence double staining was used to observe the relationship of the mast cells with SP, VIP, and SS positive nerve fibers.. On day 6 after TNBS injection, obvious ulcers occurred in the distal colon of the rats with significantly increased histamine level in the whole blood (P<0.05) but significantly decreased colonic histamine levels (P<0.05). The histamine levels in the whole blood and distal colon gradually recovered the normal levels. The mast cells significantly increased on day 16 (P<0.05) and maintained the high level till day 21. The distribution of mast cells was altered after TNBS injection, and the cells were found to aggregate in the myenteric region. SP levels in the distal colon significantly increased on day 11 (P<0.05) and maintained the high level till day 21. Immunofluorescence double staining revealed numerous mast cells close to the SP- and VIP-positive nerve fibers at different time points after TNBS injection. VIP positivity and the number of VIP-positive nerve fibers in the myenteric region were markedly increased, but no mast cells were observed in association with SP- and VIP-positive nerve fibers. The distribution of MC was not found to associate with the SS-positive nerve fibers.. The mast cells and histamine released by them, as well as parasecretion of SP and VIP, participate in tissue damage by TNBS-induced colitis. Bidirectional neuroimmunomodulation of the mast cells, SP and VIP have important effect on the development of TNBS-induced colitis.

Topics: Animals; Colitis, Ulcerative; Disease Models, Animal; Male; Mast Cells; Rats; Rats, Sprague-Dawley; Substance P; Trinitrobenzenesulfonic Acid; Vasoactive Intestinal Peptide

Therapy of uncomplicated nonspecific ulcerative colitis with artrofoon effectively reduces the duration and number of relapses. During remissions, the count of apudocytes, serotonin-, melatonin-, vasointestinal peptide-producing, and mast cells and the parameters of cell homeostasis against the background of artrofoon therapy were much closer to the normal than during treatment with salofalk.

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal; Colitis, Ulcerative; Female; Humans; Male; Mast Cells; Melatonin; Mesalamine; Middle Aged; Serotonin; Vasoactive Intestinal Peptide; Young Adult

Glucagon-like peptide-2 (GLP-2) is an important regulator of nutritional absorptive capacity with anti-inflammatory actions. We hypothesized that GLP-2 reduces intestinal mucosal inflammation by activation of vasoactive intestinal polypeptide (VIP) neurons of the submucosal plexus. Ileitis or colitis was induced in rats by injection of trinitrobenzene sulfonic acid (TNBS), or colitis was induced by administration of dextran sodium sulfate (DSS) in drinking water. Subsets of animals received (1-33)-GLP-2 (50 mug/kg sc bid) either immediately or 2 days after the establishment of inflammation and were followed for 3-5 days. The involvement of VIP neurons was assessed by concomitant administration of GLP-2 and the VIP antagonist [Lys(1)-Pro(2,5)-Arg(3,4)-Tyr(6)]VIP and by immunohistochemical labeling of GLP-2-activated neurons. In all models, GLP-2 treatment, whether given immediately or delayed until inflammation was established, resulted in significant improvements in animal weights, mucosal inflammation indices (myeloperoxidase levels, histological mucosal scores), and reduced levels of inflammatory cytokines (IFN-gamma, TNF-alpha, IL-1beta) and inducible nitric oxide synthase, with increased levels of IL-10 in TNBS ileitis and DSS colitis. Reduced rates of crypt cell proliferation and of apoptosis within crypts in inflamed tissues were also noted with GLP-2 treatment. These effects were abolished with coadministration of GLP-2 and the VIP antagonist. GLP-2 was shown to activate neurons and to increase the number of cells expressing VIP in the submucosal plexus of the ileum. These findings suggest that GLP-2 acts as an anti-inflammatory agent through activation of enteric VIP neurons, independent of proliferative effects. They support further studies to examine the role of neural signaling in the regulation of intestinal inflammation.

Topics: Animals; Anti-Inflammatory Agents; Colitis, Ulcerative; Dextran Sulfate; Disease Models, Animal; Enteric Nervous System; Glucagon-Like Peptide 2; Ileitis; Male; Neurotensin; Rats; Rats, Sprague-Dawley; Recombinant Fusion Proteins; Trinitrobenzenesulfonic Acid; Vasoactive Intestinal Peptide

The neuropeptide vasoactive intestinal peptide (VIP) is involved in the neuroimmunomodulation of the intestine. In the present study, specimens from the sigmoid colon of ulcerative colitis (UC) and non-UC patients were examined for immunohistochemistry and in vitro receptor autoradiography. Marked occurrence of VIP binding was observed in the mucosa. However, there were very low levels of binding in areas showing pronounced inflammation/derangement. The study shows that marked derangement of the mucosa leads to a distinct decrease in VIP binding. Thus, it is possible that a decrease in trophic and anti-inflammatory VIP effects occurs in areas exhibiting a very marked inflammation.

Topics: Adult; Aged; Aged, 80 and over; Autoradiography; Biomarkers; Colitis, Ulcerative; Female; Gastric Mucosa; Humans; Immunohistochemistry; Inflammation; Intestinal Mucosa; Male; Middle Aged; Receptors, Vasoactive Intestinal Peptide; Vasoactive Intestinal Peptide

Morphological and functional changes in the enteric nervous system (ENS) have been reported in inflammatory bowel diseases but it is still uncertain whether neurochemical coding of myenteric neurones is altered in ulcerative colitis (UC).. In this study we investigated transmitter co-localisation in myenteric neurones of normal colon and the colon of patients with UC.. Choline acetyltransferase (ChAT), neurone specific enolase (NSE), vasoactive intestinal peptide (VIP), and substance P (SP) were detected by immunohistochemical methods in whole mounts of colonic myenteric plexus of UC patients (n=10) and controls (n=8).. The proportion of ChAT positive and VIP positive neurones relative to the NSE population did not differ in inflamed (33.3% and 9.3%, respectively) and non-inflamed segments (33.6% and 9.7%) of UC colon compared with controls (35.0% and 6.9%). The proportion of SP positive neurones was significantly larger in both inflamed (15.5%) and non-inflamed (20.3%) segments than in controls (5.9%). Analysis of changes in subpopulations showed that 26.9% of neurones were only ChAT positive in controls but that the proportion was significantly smaller in inflamed (18.8%) and non-inflamed (15.8%) areas of UC. The proportions of neurones containing ChAT and SP were significantly higher in inflamed (11.8%) and non-inflamed (13.9%) areas than in controls (5.0%).. Remodelling of myenteric neurones in UC involves a shift from mainly cholinergic to more SP positive innervation. This effect may constitute part of the neuronal basis for the motility disturbances observed in UC.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Case-Control Studies; Choline O-Acetyltransferase; Colitis, Ulcerative; Colon; Female; Gastrointestinal Motility; Humans; Immunohistochemistry; Male; Middle Aged; Muscle, Smooth; Myenteric Plexus; Neurons; Neurotransmitter Agents; Phosphopyruvate Hydratase; Substance P; Vasoactive Intestinal Peptide

The double immunofluorescence technique was used to examine the distribution and interrelationship between LENK- and VIP-immunoreactive nerve fibres within the muscle layer and myenteric plexus of the large intestine in a young female patient (aged 17 years) suffering from colitis ulcerosa activa (CUA). As the CUA was found to be totally drug-resistant, a pancolotomy was performed by means of the Soave technique. Varicose nerve fibres, immunoreactive either to LENK or VIP, but not to both substances simultaneously, were found in all fragments of the bowel studied. A striking feature was their distribution pattern within the studied layers. In all cases LENK-IR fibres were closely accompanied by VIP-IR terminals. The density of the examined fibres depended on the bowel fragment studied, and was the greatest in the sigmoid colon, descending colon and rectum, while the lowest number was found in the caecum. The results of the present study may thus be indicative for the involvement of LENK- and VIPIR nerve fibres in the control of bowel functions during CUA, possibly on the basis of a "cross-talk" between terminals running in close vicinity to each other.

Topics: Adolescent; Colitis, Ulcerative; Drug Resistance; Enkephalin, Leucine; Female; Fluorescent Antibody Technique, Indirect; Humans; Intestine, Large; Myenteric Plexus; Nerve Fibers; Vasoactive Intestinal Peptide

Many studies have indicated changes in neuropeptides in inflammatory bowel disease (IBD), but with contradictory results. Nerve growth factor also has a potential role in the maintenance of enteric nerves and may be associated with IBD. A quantitative immunohistochemical method was used to measure area density of immunoreactive nerves in the colonic mucosa of surgical specimens. No significant differences in immunoreactivity for substance P, vasoactive intestinal polypeptide, growth associated protein 43, and the neurotrophin receptor p75 were seen in the control, Crohn's, and ulcerative colitis groups. Compared to age-matched normal colon (N = 18), there was an increase in neutrophil number in Crohn's (P < 0.05) and ulcerative colitis (P < 0.01) (both N = 9). There were positive correlations (P < 0.05) between neutrophil number and growth associated protein, between p75 and substance P immunoreactive nerves in ulcerative colitis, and between p75 and vasoactive intestinal polypeptide in Crohn's specimens. These data indicate a link between the immunologic and nervous systems in IBD.

Topics: Adult; Aged; Colitis, Ulcerative; Colon; Crohn Disease; Female; GAP-43 Protein; Humans; Immunohistochemistry; Intestinal Mucosa; Male; Middle Aged; Nerve Fibers; Nerve Growth Factors; Neuropeptides; Neutrophils; Receptor, Nerve Growth Factor; Substance P; Vasoactive Intestinal Peptide

Ulcerative colitis is a chronic inflammatory condition characterized by an altered intestinal immunoinflammatory response. Since increasing evidence indicates that neuropeptides play a key role in the regulation of gastrointestinal immune function, the aims of this study were: a) to determine tissue and plasma levels of Vasoactive Intestinal Polypeptide, Substance P, and Calcitonin Gene-Related Peptide in patients with ulcerative colitis, and b) to ascertain whether a relationship exists between tissue concentrations of neuropeptides and the histological grading of mucosal inflammation.. A total of 29 patients with active and 39 with inactive ulcerative colitis, and 16 control subjects took part in the study. Biopsy specimens of colonic mucosa and blood samples were obtained from each subject, and neuropeptide concentrations were measured by sensitive and specific radioimmunoassays.. Both Vasoactive Intestinal Polypeptide and Substance P concentrations were found to be significantly reduced in endoscopic biopsy specimens of patients with ulcerative colitis compared to controls (p < 0.01 and p = 0.05, respectively), and the reduction appeared to be related to the degree of mucosal inflammation; in contrast, Calcitonin Gene-Related Peptide tissue levels were unchanged. In addition, there was no significant difference in the neuropeptide plasma levels between ulcerative colitis patients and control subjects.. Taken together, our results suggest that the reduction of Vasoactive Intestinal Polypeptide and Substance P is probably a secondary phenomenon, correlated with the degree of mucosal inflammation; whatever the mechanism, the decreased availability of these neuropeptides in the local microenvironment may play an important role in the pathogenesis of ulcerative colitis, by affecting many components of the normal immune response. Moreover, based on our data, the measurement of neuropeptide plasma concentrations does not appear to be a useful tool to monitor disease activity.

Topics: Adult; Aged; Biomarkers; Biopsy; Calcitonin Gene-Related Peptide; Colitis, Ulcerative; Colon; Colonoscopy; Female; Humans; Intestinal Mucosa; Male; Middle Aged; Radioimmunoassay; Rectum; Severity of Illness Index; Substance P; Vasoactive Intestinal Peptide

Recent studies suggest that the intestinal polypeptides substance P (SP) and vasoactive intestinal polypeptide (VIP) play a role in the bowel inflammatory processes. The aim of this study was to evaluate the distribution of SP and VIP immunoreactivities in the ileal pouch of the patients with ulcerative colitis (UC). Thirty-six patients underwent clinical evaluation, endoscopy, and histological examinations. Samples were taken from normal ileum (N = 9), ileum of UC patients (N = 9), normal ileal pouch (N = 9) and pouchitis (N = 9). SP- and VIP-containing nerve fibers were visualized in sections processed for immunofluorescence microscopy. The number and intensity of SP and VIP immunoreactivities were subjected to quantitative scoring. On samples from all groups lamina propria contained fibers showing bright immunofluorescence for SP and VIP. The number and intensity of SP immunoreactive nerve fibers were markedly increased in pouchitis as compared to normal pouch (P < 0.005), to ileum of UC patients (P < 0.001), and to normal ileum (P < 0.05). The number and intensity of VIP-immunoreactive nerve fibers in the lamina propria were markedly increased in pouchitis patients and in those having a normal pouch as compared to pooled values of ileum of UC patients and normal ileum (P < 0.05). The results suggest that SP, which may play a role in mediating inflammatory processes, is increased in pouchitis and that VIP, which may contribute to the regulation of intestinal motility, is increased in the pouch.

Topics: Adult; Aged; Colitis, Ulcerative; Female; Humans; Ileum; Immunohistochemistry; Inflammation; Male; Middle Aged; Nerve Fibers; Postoperative Complications; Proctocolectomy, Restorative; Substance P; Vasoactive Intestinal Peptide

Recent studies suggest that substance P (SP), vasoactive intestinal polypeptide (VIP), and mast cells play a role in inflammatory processes of the bowel. The aim of this study was to evaluate the distribution of SP and VIP immunoreactivities and to count mast cells in the ileal pouch of patients, who had pouchitis after restorative proctocolectomy performed for treatment of ulcerative colitis (UC), and to compare the findings in the same patients after a follow-up period. Nine patients with pouchitis underwent clinical evaluation, endoscopy of the pouch, and histological examination, which were repeated after the follow-up period of 14 months on average. The number and intensity of SP- and VIP-immunoreactive nerve fibers were visualized by immunofluorescence microscopy and subjected to quantitative scoring, and the number of mast cells per unit area was counted. The results were compared to the histological findings and the clinical status. Lamina propria contained fibers showing bright immunofluorescence for SP and VIP. The mean fluorescence intensity score of SP-immunoreactive nerve fibers in the lamina propria remained similar after the follow-up period (2.99 +/- 0.79 and 2.06 +/- 0.82, NS). SP-immunoreactive innervation correlated with the grade of acute (R2 = 0.5396, P = 0.0242) and chronic inflammation (R2 = 0.4561, P = 0.0459), while SP and VIP immunoreactivity, mast cell count, and histological changes did not correlate with the clinical status. The present study demonstrates an increase in the density of SP-immunoreactive nerve fibers in inflamed ileal pouch mucosa of clinically asymptomatic pouchitis patients. These results raise the possibility of therapeutic interference of SP-related processes in treatment of pouchitis.

Topics: Adult; Biopsy; Cell Count; Colitis, Ulcerative; Endoscopy, Gastrointestinal; Female; Follow-Up Studies; Humans; Ileum; Immunohistochemistry; Inflammation; Male; Mast Cells; Middle Aged; Nerve Fibers; Postoperative Complications; Proctocolectomy, Restorative; Substance P; Vasoactive Intestinal Peptide

The availability of colon provides a ready source of human neurons. Among the products of nerve cell bodies, vasoactive intestinal peptide is a neuropeptide that serves as a marker of non-adrenergic, non-cholinergic inhibitory nerves in colon. These nerves have been proposed to be involved in regulation of immune function, secretion, and smooth muscle function. In previous work, we identified decreased tissue levels of vasoactive intestinal peptide in a disorder of chronic colonic mucosal inflammation, ulcerative colitis. We hypothesized that diminished gene expression of vasoactive intestinal peptide could result in decreased tissue levels of this neuropeptide. Sigmoid colon was obtained at surgery from controls (n = 6) and patients with ulcerative colitis (n = 6). Vasoactive intestinal peptide mRNA was quantified by Northern blot hybridization and tissue levels of vasoactive intestinal peptide were determined by radioimmunoassay. Tissue vasoactive intestinal peptide was decreased only in the mucosal-submucosal layer of ulcerative colitis (p = .02). There was a single 1.7 kbase vasoactive intestinal peptide transcript identified in both control colon and ulcerative colitis. Normalized vasoactive intestinal peptide mRNA levels were increased by 260% in ulcerative colitis compared to controls (p < .01). These observations suggest that decreased vasoactive intestinal peptide gene expression or abnormal post-transcriptional processing are not primary defects in this disorder of chronic inflammation. The findings support the alternative hypothesis that axonal degeneration in ulcerative colitis could result in increased expression of neuronal vasoactive intestinal peptide mRNA.

Topics: Adult; Aged; Blotting, Northern; Colitis, Ulcerative; Colon; Female; Gene Expression; Humans; Intestinal Mucosa; Male; Middle Aged; RNA, Messenger; Vasoactive Intestinal Peptide

The distribution abnormality of vasoactive intestinal polypeptide-containing nerves (VIP-nerves) and substance P-containing nerves (SP-nerves) was immunohistochemically investigated in the colonic mucosa with inflammatory bowel disease (IBD) in relation to colonic glands and blood vessels in the lamina propria. In active ulcerative colitis (UC), VIP- and SP-nerves decreased in severe inflammatory lesions. VIP-nerves were almost absent particularly around crypt abscesses. Even in resolving and quiescent UC, VIP-nerves still decreased, depending on the decrease of glands and blood vessels. On the other hand, both nerves increased in some hypervascular lesions. In the uninvolved mucosa of UC, they did not change their distribution. In Crohn's disease, the distribution abnormality of both nerves resembled that of UC. These results suggest that the changes in VIP- and SP-nerve distributions in the mucosa with IBD are subsequent to mucosal inflammation and damage. However, these peptides are known to be immunoregulators, and their distribution abnormalities may induce the disorder of immunoregulation in the IBD mucosa and cause the mucosal damage and/or chronicity.

Topics: Adolescent; Adult; Aged; Colitis, Ulcerative; Colon; Crohn Disease; Female; Humans; Immunohistochemistry; Intestinal Mucosa; Male; Middle Aged; Nerve Fibers; Neuropeptides; Substance P; Vasoactive Intestinal Peptide

Neuropeptides form a part of the brain-gut axis which may regulate gastrointestinal functions, including immune regulation. Various changes in the neuropeptides--most important, vasoactive intestinal peptide and substances P (VIP and SP)--have been described in inflammatory bowel disease. We employed a sensitive immunoperoxidase (avidin-biotin-peroxidase complex) technique, using anti-VIP and anti-SP antibodies to localize and compare the distribution of VIP and SP in the colon. Colon specimens from 19 normal subjects, eight patients with ulcerative colitis (UC), and eight with Crohn's disease (CD) were used. In the normal colon, VIP and SP immunoreactivity (IR) were localized in the muscularis mucosa, circular muscles, walls of blood vessels, nerve fibers, and some distinct cells, probably enterochromaffin cells. SP-IR was also present in the epithelial cells, mainly along the basolateral domain. VIP-IR was considerably diminished at all locations in patients with UC and CD. However, the SP-IR was increased in UC in the colonic epithelial cells along the basolateral areas. The SP-IR was intense in patients with CD, in the epithelium, the granulomas, cells lining the mucosal fissure, and in the muscle layers. In contrast to normals, SP-IR in patients with CD was observed both in the longitudinal and circular muscles. We conclude that VIP-IR and SP-IR are distributed widely in the mucosa, submucosa, and in the circular muscle in normal colon. VIP-IR is decreased in UC and CD, whereas SP-IR is increased in both, but more so in CD.

Topics: Colitis, Ulcerative; Colon; Crohn Disease; Humans; Immunoenzyme Techniques; Inflammatory Bowel Diseases; Reference Values; Substance P; Vasoactive Intestinal Peptide

We describe a case of a tumour of the sigmoid colon with hepatic metastases in a patient with previously documented ulcerative colitis. A diagnosis of metastatic vipoma was made on the basis of high plasma levels of vasoactive intestinal polypeptide (VIP). Profuse diarrhoea and profound metabolic upset were corrected by the use of a somatostatin analogue SMS 201-995, whilst conventional cytotoxic therapy produced a significant tumour response with return of the plasma VIP level to normal.

Topics: Adenoma, Islet Cell; Adult; Antineoplastic Combined Chemotherapy Protocols; Colitis, Ulcerative; Colostomy; Combined Modality Therapy; Female; Humans; Liver Neoplasms; Octreotide; Pancreatic Neoplasms; Sigmoid Neoplasms; Streptozocin; Vasoactive Intestinal Peptide; Vipoma

The study was undertaken to examine regional differences in the concentrations of five regulatory peptides in the human colonic mucosa. Biopsies were obtained during routine colonoscopy from 33 patients whose colonic mucosa was macroscopically and histologically normal. Regulatory peptides were extracted, and measured by specific radioimmunoassays. Concentrations of three peptides that are present predominantly in endocrine cells within colonic mucosa increased significantly towards the rectum: Mean concentrations of peptide YY, enteroglucagon, and somatostatin were about three times greater in the rectum than in the cecum. However, concentrations of two peptides that are present in mucosal nerve fibers diminished significantly towards the rectum: Mean rectal concentrations of vasoactive intestinal peptide and peptide histidine methionine were both about 0.6 of mean cecal concentrations. Concentrations of all five peptides were lower in biopsies taken from colonic polyps than in normal colonic mucosa. Regional differences in colonic mucosal concentrations of regulatory peptides probably reflect differences in the physiological functions of different parts of the colon.

Topics: Adolescent; Adult; Aged; Cecum; Colitis, Ulcerative; Colon; Colonic Polyps; Crohn Disease; Female; Gastrointestinal Hormones; Glucagon-Like Peptides; Humans; Intestinal Mucosa; Male; Middle Aged; Peptide PHI; Peptide YY; Peptides; Radioimmunoassay; Rectum; Somatostatin; Vasoactive Intestinal Peptide

After colectomy, continent ileal reservoirs are an accepted alternative to conventional ileostomy for patients with ulcerative colitis. To assess the effect of these reservoirs on digestive function, circulating and morphologic gut endocrine responses were measured in patients with a continent ileostomy or with a pelvic pouch and compared to patients with conventional ileostomy, with active ulcerative colitis and healthy controls. Eight subjects were studied in each group. Basal and postprandial plasma gastrin, enteroglucagon, neurotensin, vasoactive intestinal polypeptide, insulin, pancreatic glucagon, and pancreatic polypeptide in both groups with ileal reservoirs were equivalent to controls. Basal plasma motilin and postprandial plasma gastric inhibitory polypeptide were raised in ileal reservoir patients, but similar changes also occurred in ulcerative colitis patients and those with conventional ileostomy. In one half of patients, cell populations of enteroglucagon, peptide YY, and neurotensin were decreased in pouch mucosa that corresponded with the presence of mucosal inflammation. On the other hand, with pouch inflammation vasoactive intestinal polypeptide immunoreactive nerves were increased and a proportion of the fibres were moderately coarsened. Mucosal concentrations of vasoactive intestinal polypeptide did not, however, exceed that of controls. After an ileal reservoir sufficient reserve remains for gut hormone release into the circulation, suggesting compensation for the presence of a reservoir and the absence of a colon; circulating hormone changes do occur but are consequent upon previous ulcerative colitis. Reservoirs may show neuromorphologic alterations that appear to be related to mucosal inflammation.

Topics: Adult; Colitis, Ulcerative; Eating; Female; Gastrointestinal Hormones; Humans; Ileitis; Ileostomy; Ileum; Male; Middle Aged; Neurotensin; Pancreatic Hormones; Postoperative Complications; Vasoactive Intestinal Peptide

Circulating levels of vasoactive intestinal peptide (VIP) in plasma were measured in gauging activity in inflammatory bowel disease (IBD). One hundred-fifteen adult IBD patients were studied cross-sectionally and prospectively, 48 with ulcerative colitis (UC) and 67 with Crohn's disease (CD). Sequential samples of plasma were assayed for VIP by specific radioimmunoassay. Sixty males and 55 females, ranging in age from 22 to 76 years were studied over six months. The results revealed a strong, positive association between VIP levels and clinical activity, both at baseline (r = 0.38, P less than 0.001) and follow-up (r = .41, P less than 0.001). The ability of the VIP immunoassay to gauge clinical activity was also evaluated where VIP concentrations above 30 pg/ml were defined as abnormal. At baseline, sensitivity (specificity) was found to be 81% (55%). The predictive value of a positive (negative) test was 57% (80%). These estimates did not differ at follow-up. Examination of paired plasma samples from intermittently active patients revealed nearly twofold increases (P less than 0.05) in VIP concentration during active periods of disease. The data suggest that plasma VIP levels may be a valuable laboratory parameter in gauging activity in inflammatory bowel disease.

Topics: Adult; Colitis, Ulcerative; Crohn Disease; Female; Follow-Up Studies; Humans; Immunoassay; Male; Sex Factors; Vasoactive Intestinal Peptide

The sequence for peptide histidine-methionine is present within the same preprohormone as vasoactive intestinal polypeptide. Since our previous study using radioimmunoassay had demonstrated significantly decreased colonic concentrations of vasoactive intestinal polypeptide in ulcerative colitis and Crohn's colitis compared to normal colon, we determined the distribution and quantitation of peptide histidine-methionine. Fresh surgical specimens were dissected into mucosal-submucosal and muscularis externa layers prior to acid extraction and specific radioimmunoassay. One immunoreactive species that appeared to coelute with peptide histidine-methionine was separated by reverse-phase high-performance liquid chromatography. Mucosal-submucosal concentrations of peptide histidine-methionine were significantly decreased in ulcerative colitis and Crohn's colitis, compared to those in normal colon. In normal ileum and colon, linear correlation analysis showed no relationship between patient age and tissue concentrations of peptide histidine-methionine. However, a parallel decrease in molar concentrations of peptide histidine-methionine and vasoactive intestinal polypeptide in ulcerative colitis and Crohn's colitis was demonstrated by linear correlation analysis. These results are consistent with the hypothesis that peptide histidine-methionine and vasoactive intestinal polypeptide are colocalized within the same neural structures that have been altered in the idiopathic inflammatory bowel diseases.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aging; Chromatography, High Pressure Liquid; Colitis, Ulcerative; Colon; Crohn Disease; Humans; Ileum; Intestinal Mucosa; Middle Aged; Peptide PHI; Radioimmunoassay; Vasoactive Intestinal Peptide

To study hyperplasia of peptidergic nerves purported to be diagnostic of Crohn's disease, we determined the distribution and concentrations of gut neuropeptides in specimens of normal intestine, ulcerative colitis, and Crohn's disease. Tissue specimens obtained at surgery were dissected into the mucosal-submucosal and muscularis externa layers, and immunoreactive gut neuropeptides were acid-extracted for measurement by radioimmunoassay. The immunoreactive species were characterized by column chromatography. Mucosal-submucosal layer concentrations of vasoactive intestinal peptide were significantly decreased in Crohn's colitis and ulcerative colitis, while mucosal-submucosal layer concentrations of substance P were significantly increased in left-sided ulcerative colitis. Muscularis externa layer concentrations of vasoactive intestinal peptide and met5-enkephalin were decreased in left-sided Crohn's colitis. These neuropeptide concentration abnormalities did not clearly differentiate between Crohn's colitis and ulcerative colitis, and no increase in concentration of a neuropeptide diagnostic of Crohn's disease was identified.

Topics: Adult; Aged; Bombesin; Chromatography; Colitis, Ulcerative; Crohn Disease; Enkephalin, Methionine; Histocytochemistry; Humans; Intestinal Mucosa; Middle Aged; Neuropeptides; Radioimmunoassay; Substance P; Vasoactive Intestinal Peptide

Vasoactive intestinal polypeptide (VIP)-containing nerves and VIP content of endoscopic rectal biopsies from 47 patients with inflammatory bowel disease and 17 normal controls were examined by immunocytochemistry and radioimmunoassay. Immunocytochemistry revealed a consistent increase in, and abnormal appearance of, VIP nerves in patients with Crohn's disease not only those with rectal involvement but also patients with no histological evidence of rectal disease. Normal control biopsies contained 1.64 +/- 0.39 pmol VIP/mg protein as compared with 3.43 +/- 1.24 pmol VIP/mg protein in tissue from patients with rectal Crohn's disease and 5.37 +/- 1.23 pmol VIP/mg protein in those with Crohn's disease without rectal involvement. Ten of the 17 biopsies examined from ulcerative colitics showed a normal pattern of VIP innervation. Examination of the conventional histology of these biopsies showed that only areas with obvious active proctitis had increased VIP nerves and, unlike the appearance in Crohn's disease, these nerves had a normal morphology. The VIP content of these biopsies was similar to that of the controls; 1.34 +/- 0.37 pmol/mg protein.

Topics: Adolescent; Adult; Aged; Colitis, Ulcerative; Crohn Disease; Fluorescent Antibody Technique; Humans; Intestinal Mucosa; Middle Aged; Proctitis; Radioimmunoassay; Rectum; Vasoactive Intestinal Peptide

We have studied fasting levels and the response to a standard test breakfast of blood glucose and several gut hormones in 24 patients with ulcerative colitis, in 14 patients with Crohn's disease, and in 14 healthy control subjects. Patients with ulcerative colitis had significantly elevated fasting human pancreatic polypeptide (HPP) concentrations, and both basal and postprandial levels of gastrin, gastric inhibitory polypeptide (GIP), and motilin were greater than normal. In contrast, patients with Crohn's disease had normal gastrin levels but had increased fasting and postprandial levels of GIP and motilin and, in addition, of enteroglucagon, compared with controls. These patients also had greater than normal HPP concentrations 30 min after the breakfast. Normal levels of insulin, pancreatic glucagon, neurotensin, and vasoactive intestinal polypeptide were found in both groups of patients. Much remains to be known about the pathophysiology of these two debilitating diseases, and the abnormal release of gut hormones may be of importance.

Topics: Adolescent; Adult; Aged; Blood Glucose; Colitis, Ulcerative; Crohn Disease; Female; Gastric Inhibitory Polypeptide; Gastrins; Gastrointestinal Hormones; Glucagon-Like Peptides; Humans; Insulin; Male; Middle Aged; Motilin; Neurotensin; Pancreatic Polypeptide; Vasoactive Intestinal Peptide

The possible involvement of nerves containing vasoactive intestinal polypeptide in Crohn's disease was investigated by immunocytochemistry and radioimmunoassay of specimens from 17 patients with well-defined clinical and histologic features of the disease. The characteristic pattern of slender fibers, evenly distributed across the gut wall, was seen in specimens taken from controls, which consisted of (a) specimens from uninvolved areas of gut from carcinoma resection (n = 17) and (b) jejunoileal specimens obtained during bypass operation for obesity (n = 8) as well as in four of the six specimens from patients with ulcerative colitis. In contrast, this characteristic pattern was lost in all 17 patients with Crohn's disease, the pattern being replaced by thickened and more intensely immunostained fibers. These changes were consistently found in the mucosa and submucosa, and in 13 of the Crohn's disease cases, the abnormal pattern was totally transmural, involving both the myenteric and submucous plexus as well as the muscle layers. There was a > 200% increase in VIP content, as determined by radioimmunoassay, in Crohn's disease (294 +/- 29 pmol/g wet wt, mean +/- SEM) in comparison with (a) ulcerative colitis (93 +/- 5 pmol/g [P < 0.001]), and (b) controls consisting of carcinoma resection (108 +/- 39) and bypassed gut from obese patients (86 +/- 27 [P < 0.001]). At least part of the previously documented autonomic nerve changes in Crohn's disease are, thus, due to an increase in vasoactive intestinal polypeptide innervation.

Topics: Adolescent; Adult; Aged; Autonomic Nervous System; Colitis, Ulcerative; Colon; Crohn Disease; Gastrointestinal Hormones; Humans; Ileum; Immune Sera; Intestinal Mucosa; Middle Aged; Radioimmunoassay; Vasoactive Intestinal Peptide