Dysbiosis and zonulin upregulation alter gut epithelial and vascular barriers in patients with ankylosing spondylitis.

BACKGROUND: Dysbiosis has been recently demonstrated in patients with ankylosing spondylitis (AS) but its implications in the modulation of intestinal immune responses have never been studied. The aim of this study was to investigate the role of ileal bacteria in modulating local and systemic immune responses in AS. METHODS: Ileal biopsies were obtained from 50 HLA-B27+ patients with AS and 20 normal subjects. Silver stain was used to visualise bacteria. Ileal expression of tight and adherens junction proteins was investigated by TaqMan real-time (RT)-PCR and immunohistochemistry. Serum levels of lipopolysaccharide (LPS), LPS-binding protein (LPS-BP), intestinal fatty acid-BP (iFABP) and zonulin were assayed by ELISA. Monocyte immunological functions were studied in in vitro experiments. In addition the effects of antibiotics on tight junctions in human leukocyte antigen (HLA)-B27 transgenic (TG) rats were assessed. RESULTS: Adherent and invasive bacteria were observed in the gut of patients with AS with the bacterial scores significantly correlated with gut inflammation. Impairment of the gut vascular barrier (GVB) was also present in AS, accompanied by significant upregulation of zonulin, and associated with high serum levels of LPS, LPS-BP, iFABP and zonulin. In in vitro studies zonulin altered endothelial tight junctions while its epithelial release was modulated by isolated AS ileal bacteria. AS circulating monocytes displayed an anergic phenotype partially restored by ex vivo stimulation with LPS+sCD14 and their stimulation with recombinant zonulin induced a clear M2 phenotype. Antibiotics restored tight junction function in HLA-B27 TG rats. CONCLUSIONS: Bacterial ileitis, increased zonulin expression and damaged intestinal mucosal barrier and GVB, characterises the gut of patients with AS and are associated with increased blood levels of zonulin, and bacterial products. Bacterial products and zonulin influence monocyte behaviour.

Physiological relevance of food grade microcapsules: Impact of milk protein based microcapsules on inflammation in mouse models for inflammatory bowel diseases.

In order to increase beneficial effects of bioactive compounds in functional food and dietary supplements, enormous efforts are put in the technological development of microcapsules. Although these products are often tailor-made for disease susceptible consumer, the physiological impact of microcapsule uptake on the respective target consumer has never been addressed. The present study aimed to assess the relevance of this aspect by analyzing the impact of milk protein based microcapsules on experimental inflammatory bowel disease. Long-term feeding of sodium caseinate or rennet gel microcapsules resulted in significant alterations in the intestinal microbiota of healthy mice. In TNFΔARE/wt mice, a model for chronic ileal inflammation, rennet gel microcapsules resulted in further increased splenomegaly, whereas ileal inflammation was unchanged. In IL10(-/-) mice, a model for chronic colitis, both types of microcapsules induced a local increase of the intestinal inflammation. The present study is the first to demonstrate that, independent of their cargo, microcapsules have the potential to affect the intestinal microbiota and to exert unprecedented detrimental effects on disease-susceptible individuals. In conclusion, the impact of microcapsule uptake on the respective target consumer groups should be thoroughly investigated in advance to their commercial use in functional food or dietary supplements.

Capsule endoscopic findings correlate with fecal calprotectin and C-reactive protein in patients with suspected small-bowel Crohn's disease.

OBJECTIVE: Capsule endoscopy (CE) is a sensitive method for detecting inflammatory lesions in the small bowel. Such lesions may be due to Crohn's disease but also to other causes and a histological diagnosis may be difficult to achieve in the small bowel. The aim of the study was to find a possible correlation between capsule endoscopic findings, biochemical parameters, and symptoms in patients with suspected or known small-bowel Crohn´s disease. MATERIALS AND METHODS: Thirty patients with inflammatory lesions in the small bowel diagnosed by CE were included. CE findings of inflammation were graded using the Lewis score. C-reactive protein (CRP) and fecal calprotectin were used as biochemical parameters. Symptoms were graded using the Harvey-Bradshaw index. The patients were followed up after 9 months with a second CE, CRP, fecal calprotectin, and Harvey-Bradshaw index. RESULTS: There was a significant persistent correlation between endoscopic inflammation and fecal calprotectin (p = 0.003 at inclusion and p < 0.001 at follow-up). CRP was correlated to endoscopic inflammation at inclusion (p = 0.006), but not at follow-up. Symptoms were not correlated with endoscopic inflammation. CONCLUSION: Inflammatory lesions in the small bowel diagnosed by CE in patients with suspected Crohn´s disease are correlated to fecal calprotectin and CRP, but not to symptoms.

High fat diet accelerates pathogenesis of murine Crohn's disease-like ileitis independently of obesity.

BACKGROUND: Obesity has been associated with a more severe disease course in inflammatory bowel disease (IBD) and epidemiological data identified dietary fats but not obesity as risk factors for the development of IBD. Crohn's disease is one of the two major IBD phenotypes and mostly affects the terminal ileum. Despite recent observations that high fat diets (HFD) impair intestinal barrier functions and drive pathobiont selection relevant for chronic inflammation in the colon, mechanisms of high fat diets in the pathogenesis of Crohn's disease are not known. The aim of this study was to characterize the effect of HFD on the development of chronic ileal inflammation in a murine model of Crohn's disease-like ileitis. METHODS: TNF(ΔARE/WT) mice and wildtype C57BL/6 littermates were fed a HFD compared to control diet for different durations. Intestinal pathology and metabolic parameters (glucose tolerance, mesenteric tissue characteristics) were assessed. Intestinal barrier integrity was characterized at different levels including polyethylene glycol (PEG) translocation, endotoxin in portal vein plasma and cellular markers of barrier function. Inflammatory activation of epithelial cells as well as immune cell infiltration into ileal tissue were determined and related to luminal factors. RESULTS: HFD aggravated ileal inflammation but did not induce significant overweight or typical metabolic disorders in TNF(ΔARE/WT). Expression of the tight junction protein Occludin was markedly reduced in the ileal epithelium of HFD mice independently of inflammation, and translocation of endotoxin was increased. Epithelial cells showed enhanced expression of inflammation-related activation markers, along with enhanced luminal factors-driven recruitment of dendritic cells and Th17-biased lymphocyte infiltration into the lamina propria. CONCLUSIONS: HFD feeding, independently of obesity, accelerated disease onset of small intestinal inflammation in Crohn's disease-relevant mouse model through mechanisms that involve increased intestinal permeability and altered luminal factors, leading to enhanced dendritic cell recruitment and promoted Th17 immune responses.

Isolated active ileitis: is it a mild subtype of Crohn's disease?

BACKGROUND: Ileal intubation is being increasingly performed at colonoscopy and has in turn lead to an increasingly recognized subgroup of patients-those with mild terminal ileal inflammation, an entity that we have coined isolated active ileitis (IAI). The aims of this study were to define the natural history of IAI and determine if IAI shares a similar genetic and serologic profile with Crohn's disease (CD). METHODS: Patients with IAI were identified from our institution's histopathology and endoscopy databases. Cases attended for repeat colonoscopy and blood were analyzed for the expression of antineutrophil cytoplasmic antibody, anti-OmpC, anti-Saccharomyces cerevisiae antigen (ASCA) IgA, ASCA IgG, and anti-CBir antibodies and NOD2 genotyping. Age and sex-matched healthy controls, CD, and UC cases were also recruited. RESULTS: Sixty-three patients with IAI were recruited. There was no significant difference in the prevalence of antibodies between IAI cases and healthy controls for antineutrophil cytoplasmic antibody, OmpC, ASCA IgA, or ASCA IgG. The presence of all 5 antibodies was significantly higher in the CD group than the IAI group, P < 0.05. There were 28.6% of CD cases that carried one or more NOD2 variants, compared to 26.2% of the IAI cohort and 6.1% of healthy controls. Forty-three cases underwent follow-up ileocolonoscopy. Six of 43 cases (14%) had definite CD. CONCLUSIONS: A majority of IAI cases developed persistent symptoms and terminal ileal abnormalities; however, only 14% developed classical, histological, or radiological features of CD. Although patients with IAI have a low level of seropositivity, similar to healthy controls, they do share an excess of NOD2 mutations with CD cases.

Effects of infliximab therapy on transmural lesions as assessed by magnetic resonance enteroclysis in patients with ileal Crohn's disease.

BACKGROUND AND AIMS: Anti TNF therapy induces mucosal healing in patients with Crohn's disease, but the effects on transmural inflammation in the ileum are not well understood. Magnetic resonance-enteroclysis (MRE) offers excellent imaging of transmural and peri-enteric lesions in Crohn's ileitis and we aimed to study its responsiveness to anti TNF therapy. METHODS: In this multi-center prospective trial, anti TNF naïve patients with ileal Crohn's disease and with increased CRP and contrast enhanced wall thickening received infliximab 5 mg/kg at weeks 0, 2 and 6, and q8 weeks maintenance MRE was performed at baseline, 2 weeks and 6 months and assessed based on a predefined MRE score of severity in ileal Crohn's Disease. RESULTS: Twenty patients were included; of those, 18 patients underwent MRE at week 2 and 15 patients at weeks 2 and 26 as scheduled. Inflammatory components of the MRE index decreased by ≥2 points and by ≥50% at week 26 (primary endpoint) in 40% and 32% of patients (per protocol and intention to treat analysis, respectively). The MRE index improved in 44% at week 2 and in 80% at week 26. Complete absence of inflammatory lesions was observed in 0/18 at week 2 and 13% (2/15) at week 26. The obstructive elements did not change. Clinical and CRP improvement occurred as early as wk 2, but only CDAI correlated with the MRE index. CONCLUSION: Improvement of MRE occurs from 2 weeks after infliximab therapy onwards and correlates with clinical response but normalization of MRE is rare.

[Serum level of TNF-alpha receptor type II better correlates with severity of Crohn's disease than other cytokines and conventional clinical activity indicators]. / Surowicze stezenie receptora typu II dla TNF-alpha wykazuje lepsza korelacje z ciezkoscia choroby Lesniowskiego-Crohna niz inne cytokiny i konwencjonalne wskazniki aktywnosci choroby.

UNLABELLED: Crohn's disease activity index (CDAI) and serum C-reactive protein (CRP) levels are not prefect indicators of Crohn's disease severity. Magnetic resonance enteroclysis (MRE) is a method allowing simultaneous assessment of lesions involving an entire intestinal wall as well as intra- and extraintestinal spaces. This method, however, is not appropriate for monitoring the course of disease and therapeutic effects. THE AIM OF THE STUDY: To evaluate which of the extensive panel of pro- and anti- inflammatory cytokines correlates with an actual severity of CD assessed by MRE. MATERIAL AND METHODS. 57 patients with endoscopically diagnosed ileocecal form of CD (28 women, age 29 + 11 yrs, range 18-62 yrs) hospitalized in 2007-2008. The mean CDAI was 293 + 119 points, range 18-503 points and serum CRP level was 17.5 + 31 mg/l, range 0.1-122 mg/l. MRE was performed in each patient not later than 3 days after entry to the study. The summarized score was calculated using standardized protocol, assessing the intestine wall thickness and length of its involvement (ileocecal region), pattern of mural contrast enhancement, presence of fistulas or other extraintestinal lesions and enlargement of mesenteric lymph nodes. At admission the blood was taken to measure following cytokines: IL-la, IL-1 receptor antagonist, IL-6, soluble IL-6 receptor, TNF-alpha, TNF-alpha type II receptor and IL-10. RESULTS: In Spearman's correlation test the MRE score showed the strongest relationship with serum level of TNF-alpha type II receptor (r = 0.52, p < 0.001), correlating less significantly with IL-6 level (r = 0.37, p < 0.01) and CDAI (r = 0.40, p < 0.001). CONCLUSION: TNFalpha receptor type II shows better correlation with the severity of ileocecal CD (assessed by MRE) than CDAI or serum levels of other cytokines and CRP.

TNF-alpha modulates iNOS expression in an experimental rat model of indomethacin-induced jejunoileitis.

Multiple mucosal immune factors, such as TNF-alpha and IL-1beta, are thought to be key mediators involved in inflammatory bowel disease. We evaluated the role of the pro-inflammatory cytokine TNF-alpha on nitric oxide synthase (NOS) expression in indomethacin-induced jejunoileitis in rats. Jejunoileitis was induced in rats with subcutaneous injections of indomethacin (7.5 mg/kg) 24 h apart for two consecutive days, and animals were randomized into four groups. Group 1 received only indomethacin. Group 2 was treated with a daily dose of phosphodiesterase (PDE) inhibitor (theophylline or pentoxifylline) by oral gavage for 2 days before and 4 days after indomethacin. Group 3 received a single dose of anti-TNF-alpha monoclonal antibody (TNF-Ab, IP) 30 min before indomethacin. Group 4 was treated with 1 h hyperbaric oxygenation (HBO(2)) for 5 days after indomethacin. Rats were sacrificed at 12 h or 4 days after final indomethacin injection. PDE inhibitor, TNF-Ab, or HBO(2) treatment significantly decreased indomethacin-induced ulceration, myeloperoxidase activity, and disease activity index. Although indomethacin significantly increased serum TNF-alpha and nitrate/nitrite (NOx) concentrations above control values at 12 h, inducible NOS (iNOS) expression was detected only at day 4. Serum IL-1beta levels did not change at 12 h but increased 4-fold after 4 days. Indomethacin had no effect on constitutive NOS. Treatment with PDE inhibitor, TNF-Ab, or HBO(2) significantly reduced serum/tissue TNF-alpha, IL-1beta, NOx, and iNOS expression. Our data show TNF-alpha plays an early pro-inflammatory role in indomethacin-induced jejunoileitis. Additionally, down-regulation of NOx by PDE inhibitors, TNF-Ab, or HBO(2) suggests that TNF-alpha modulates iNOS expression.

Granulocyte-macrophage colony-stimulating factor autoantibodies in murine ileitis and progressive ileal Crohn's disease.

BACKGROUND & AIMS: Genetic variations that affect innate immunity increase risk of ileal Crohn's disease (CD). However, the penetrance of susceptibility genes, including NOD2, is low, suggesting additional risk factors. Neutralizing autoantibodies (Ab) against granulocyte-macrophage colony-stimulating factor (GM-CSF Ab) reduce neutrophil antimicrobial function in patients with primary alveolar proteinosis (PAP). We investigated whether GM-CSF Ab regulates neutrophil function in CD. METHODS: Serum samples from 354 adult and pediatric patients with inflammatory bowel disease (IBD) were analyzed for GM-CSF Ab and IBD markers. Levels of GM-CSF Ab were compared with patients' CD features and neutrophil function. Intestinal barrier function and nonsteroidal anti-inflammatory drug (NSAID)-induced injury were assessed in GM-CSF-null and NOD2-null mice. RESULTS: Median GM-CSF Ab levels increased from 0.4 microg/mL in control serum to 2.4 microg/mL in pediatric CD and 11.7 microg/mL in adult CD serum and were associated with ileal involvement (P<.001). Ileal location, duration of disease, and increased GM-CSF Ab levels were associated with stricturing/penetrating behavior (odds ratio, 2.2; P=.018). The positive and negative predictive values of GM-CSF Ab for stricturing/penetrating behavior were comparable with that of other IBD serum markers. CD patients with increased GM-CSF Ab had reduced neutrophil phagocytic capacity and increased accumulation of pSTAT3+ neutrophils in the affected ileum. GM-CSF-null mice and NOD2-null mice in which GM-CSF was neutralized had defects in mucosal barrier function and developed a transmural ileitis following NSAID exposure. CONCLUSIONS: GM-CSF regulates ileal homeostasis in CD and in mouse models. CD patients with increases in serum GM-CSF Ab might benefit from GM-CSF administration.

Fasting plasma carotenoids concentrations in Crohn's and pancreatic cancer patients compared to control subjects.

Carotenoids are colored molecules that are widespread in the plant kingdom, but animals cannot synthesize them. Carotenes are long, apolar molecules which require fully functioning digestive processes to be absorbed properly. Hence they could be interesting markers of intestinal absorption and digestion. Indeed, only few tests are available to assess these processes and only the D-xylose tolerance test is routinely used. However D-xylose is a sugar that tests only the absorption of water-soluble compounds and it only tests duodenal absorption. In this study, we have evaluated carotenoids as markers of digestion and absorption. We compared fasting plasma carotenoids concentrations in 21 control subjects, 20 patients with Crohn's disease, and 18 patients with pancreatic cancer. Crohn's disease alters intestinal absorption while pancreatic cancer decreases pancreatic enzyme secretion thus impairing digestion. Results show that all carotenoids are significantly lower in Crohn's and cancer patients as compared to control subjects and the multifactorial analysis shows that this decrease is mostly independent of dietary intake. Interestingly, maldigestion as seen in pancreatic cancer more strongly influences plasma lutein and lycopene concentrations while malabsorption in Crohn's disease acts on other carotenoids. Thus carotenoids could be interesting alternatives for testing and following patients that are suspected of having malabsorption or maldigestion syndromes.

Enhanced glucose-dependent glucagon-like peptide-1 and insulin secretion in Crohn patients with terminal ileum disease is unrelated to disease activity or ileal resection.

BACKGROUND: Enhanced secretion of glucagon-like peptide-1 (GLP-1) has been reported in patients with Crohn disease (CD). However, the correlation between the enteropancreatic axis and the activity of CD remains unclear. METHODS: Plasma glucose, insulin, GLP-1 levels and insulin sensitivity were determined before and after oral glucose tolerance tests in 13 patients with CD of the terminal ileum, in 13 patients after resection of the terminal ileum and in 7 healthy controls. Basal and stimulated insulin sensitivities were determined using the homeostasis model assessment (HOMA) and the insulin sensitivity index (ISI) methods, respectively. RESULTS: Basal and stimulated glucose levels were comparable in patients and controls. The peak stimulated GLP-1 secretion was significantly higher in the patient group compared to controls: 12.2 +/- 1.24 pM/L and 8.1 +/- 1.72 pM/L, respectively, P=0.03. This was associated with 52% increased overall insulin secretion in the patients' group as compared to controls (P=0.007) and a higher peak insulin response: 63.5 +/- 9.69 mU/L and 41.5 +/- 6.85 mU/L for patients and controls, respectively, P=0.04. Operated patients had similar GLP-1 levels but higher peak and overall insulin secretions compared with those in non-operated patients (P=0.01). Fasting and stimulated insulin sensitivities were reduced only in patients with ileal resection as compared to controls: P=0.01 and P=0.05, respectively. No correlation was found between the CD activity index and GLP-1 or insulin secretion. CONCLUSIONS: CD of the terminal ileum is associated with enhanced glucose-dependent GLP-1 secretion, which is unrelated to disease activity or ileal resection.

Risk factors for vitamin D deficiency in patients with Crohn's disease.

BACKGROUND: Although the pathogenesis of osteopenia in Crohn's disease is not established, vitamin D deficiency is thought to be an important risk factor. However, little is known about the prevalence of vitamin D deficiency in patients with Crohn's disease in Japan. This study aimed to clarify the prevalence of vitamin D deficiency in patients with Crohn's disease in Japan and to examine the possible causes of the deficiency. METHODS: We investigated serum 25-hydroxyvitamin D (25-OHD) levels, various laboratory parameters, and patient histories in 33 outpatients (25 men, 8 women; median age, 37 years; range, 26-57 years) and 15 age- and sex-matched healthy controls (8 men, 7 women; median age, 37 years; range, 24-57 years) and assessed risk factors for vitamin D deficiency. RESULTS: Although patients with Crohn's disease did not have significantly lower serum concentrations of 25-OHD than controls, 9 of 33 patients (27.3%) were considered vitamin D deficient (serum 25-OHD level 15 years) and who have been in the active stage of the disease for long periods.

Frequently relapsing Crohn's disease is characterized by persistent elevation in interleukin-6 and soluble interleukin-2 receptor serum levels during remission.

We examined immune and inflammatory activation during remission in patients with Crohn's disease who presented with various clinical profiles (prolonged remission vs. relapsing disease). Thirty-six patients with at least 3 years' follow-up starting from a remission period were studied retrospectively. Relapses were defined by a retrospective calculation of the Crohn's disease activity index or by the clinical judgement of the physicians in charge of the patients. Disease course over the study period was assessed by the mean number of annual relapses. Analysis used measurements during remission of the following: erythrocytes sedimentation rate, relative lymphocytosis, acid alpha1-glycoprotein, interleukin-6 (IL-6), and soluble interleukin-2 receptor (sIL-2R) serum levels. During the study period 21 patients experienced at least one relapse and 15 did not. Mean serum levels of sIL-2R and mean relative lymphocytosis in remission significantly discriminated between relapsing and nonrelapsing patients. Only the mean sIL-2R serum level was selected by multivariate analysis, with a cutoff value of 82 pM/1 (sensitivity of 76% and specificity of 80%). The only features correlated with mean number of annual relapses in the relapsing patients were mean serum levels of sIL-2R (r=0.58, P=0.015) and IL-6 in remission (r=0.45, P=0.039). Multivariate analysis demonstrated statistical significance only for the mean serum level of IL-6 (P=0.014). In Crohn's disease the persistent elevation in sIL-2R serum levels during remission corresponds to chronic active disease, while high serum levels of IL-6 in these patients is associated with a high frequency of relapse.

Intestinal ulceration, obstruction, and haemorrhage in congenital syphilis.

Intestinal obstruction and bleeding are uncommon complications of congenital syphilis (CS). A VDRL-positive infant developed incomplete intestinal obstruction and rectal bleeding. Despite conservative management, his symptoms continued. At laparotomy, terminal ileal inflammation and stenosis were demonstrated. He underwent ileal resection and primary end-to-end anastomosis with resolution of his symptoms. Histopathological examination demonstrated heavy plasmacytic infiltration of the lamina propria and submucosa with ulceration of the mucosa, consistent with syphilitic ileitis. This report documents for the first time bleeding from ileal ulcers associated with intestinal obstruction in CS and highlights an unusual presentation of the disease.

Elevated plasma leptin concentrations in early stages of experimental intestinal inflammation in rats.

BACKGROUND: Although leptin, an adipocyte derived hormone which regulates food intake and energy balance, is released after injections of tumour necrosis factor (TNF) and interleukin 1, plasma concentrations have not been characterised in chronic inflammation. Leptin may contribute to the anorexia and body weight loss associated particularly with the acute stages of inflammatory bowel disease. AIMS: To investigate plasma leptin concentrations during the time course of intestinal inflammation in different animal models. METHODS: Plasma leptin was measured at different time points in rats with trinitrobenzene sulphonic acid (TNBS) induced colitis, indomethacin induced ileitis, or endotoxic shock caused by lipopolysaccharide (LPS). Systemic TNF-alpha was also measured during acute inflammation. RESULTS: Plasma leptin concentrations increased fourfold eight hours after induction of TNBS colitis (p<0.0001) and twofold after administration of ethanol alone (p<0.02). Plasma leptin responses throughout the first post-treatment day were correlated with myeloperoxidase activity and gross damage scores. Similar leptin overexpression was observed in indomethacin induced ileitis and in rats with endotoxic shock. Plasma concentrations were lower in TNBS treated rats than in controls on day 5 before reaching a similar concentration on day 14. Anorexia and body weight loss were observed during the first four days post-TNBS. A significant increase in systemic TNF-alpha was only detected in LPS treated rats. CONCLUSION: Elevated plasma leptin concentrations, correlated with the degree of inflammation and associated with anorexia, were induced in rats during the early stages of experimental intestinal inflammation but proved transient; this might account for discrepancies in recent results concerning concentrations in patients with inflammatory bowel diseases.

Computed tomography of bowel wall in patients with Crohn's disease: relationship of inflammatory activity to biological indices.

Bowel wall thickening in Crohn's disease can be demonstrated by Computed Tomography. The aim of this investigation was to correlate different patterns of bowel wall thickening, detected with Computed Tomography, with serological parameters of activity of Crohn's disease. Thirty-eight patients (24 males, 14 females, aged 21 to 62 years) were studied. Patients were divided into 3 groups according to Computed Tomography appearance of bowel wall: 1) homogeneous symmetrical thickening of wall; 2) bowel showing a layer of submucosal low attenuation; 3) scarred narrowing of wall producing stenosis. A patient was considered to have biochemically active disease if at least 2 of the following parameters were abnormal: ESR, C-reactive protein, seromucoids, serum albumin, serum alpha-2 globulin. The first group comprised 20 patients (16 active disease, 4 inactive) and the second group 13 (all inactive); the 2 groups showed a significant difference (Fisher exact test: p < 0.0005) in biological activity. Since only 5 patients belonged to the third group (3 active, 2 inactive disease), no definite conclusion can be drawn on the possible correlation between this Computed Tomography pattern and activity of disease. Results shows a correlation between Computed Tomography patterns of bowel wall disease and biochemical activity of Crohn's disease.

Tumor necrosis factor/cachectin in Crohn's disease. Relation of serum concentration to disease activity.

Inflammatory mediators seem to be involved in the pathogenesis of Crohn's disease. Tumor necrosis factor is a primary mediator of inflammatory responses which causes metabolic effects related to tissue wasting. The aims of this study were to establish the presence of tumor necrosis factor in Crohn's disease patients, to determine of its serum levels reflect disease activity and to examine the relationship if this cytokine with other assessments of the activity of the disease. Serum concentration of tumor necrosis factor, measured with a biological assay, was significantly raised in 56 Crohn's disease patients (201 determinations) as compared with 44 controls (P < 0.0001). Patients with inactive disease had significantly lower tumor necrosis factor levels (3.58 +/- 0.55 ng/mL) as compared to patients with active disease (8.17 +/- 1.01 ng/mL). There was a significant correlation between serum tumor necrosis factor concentration and disease activity (r = 0.237, P < 0.002). Higher tumor necrosis factor levels were detected in patients with colonic involvement (ileocolitis and colitis) as compared with ileal localizations, and the difference was significant (t = 2.16, P < 0.05). Besides, it correlated negatively with albumin, haemoglobin and cholesterol.

[Value of alpha-1-antitrypsin and thrombocytes in the assessment of inflammatory activity in Crohn disease]. / Wertigkeit von alpha-1-Antitrypsin und Thrombozyten zur Beurteilung der entzündlichen Aktivität des Morbus Crohn.

In 40 patients with Crohn's disease the subsequent parameters were determined in relation to the endoscopic features (group A: no or slight activity respectively [n = 26]; group B: severe inflammation of the mucosa [n = 14]; group C: patients of group B after four-weeks treatment): Crohn's disease activity index (CDAI), van Hees activity index (VHAI), C-reactive protein (CRP), ESR (erythrocytic sedimentation rate), albumin, hematocrit, platelets, alpha-1-antitrypsin (A1AT), antithrombin III, fibrinogen, clotting factors V and VIII. The hemostaseological tests were compared to the data of 16 healthy controls. The results showed significant differences regarding the mean values of CRP, ESR, albumin, CDAI, VHAI, platelets and A1AT between group A, B and C. No influence of localization or duration of the disease, age or sex could be shown by multivariate analysis. The highest test efficacy to discriminate between patients of group A and B was determined for VHAI (81.1%) and alpha-1-antitrypsin (78.4%). CDAI, platelet count, ESR (each 75.7%), CRP (70.3%) and hematocrit were less efficient. Levels of fibrinogen (59.4%) and clotting factors V (59.4%) and VIII (64.8%) were much less important. In conclusion A1AT and platelet count should be regarded as helpful tests in the evaluation of the inflammatory activity in Crohn's disease.

Erythrocytic sedimentation rate as a measure of clinical activity in inflammatory bowel disease.

To assess the reliability of the erythrocytic sedimentation rate (ESR) as a measure of clinical activity in inflammatory bowel disease, we analyzed the correlations of ESR with a global assessment of clinical activity in 77 patients with varying extents of Crohn's disease and ulcerative colitis. Analysis of all 141 ESR determinations in all 77 patients showed a highly significant correlation between mean ESR and clinical activity score (r = 0.54, p less than 0.001). Analysis of 133 ESR determinations in these 77 patients when their disease activity was either mild, moderate, or severe showed some significant differences among certain disease categories. The highest mean ESRs were in patients with the most extensive colon involvement (Crohn's colitis 40.7 +/- 3.3, universal ulcerative colitis 31.0 +/- 3.9), whereas the lowest mean ESRs were in patients with the most limited disease (ulcerative proctitis and proctosigmoiditis 19.2 +/- 2.1). The rate of increase in ESR with progressively increasing clinical activity from mild to moderate was the same in all disease categories, with the exception of Crohn's disease limited to the small bowel (ileitis or jejunoileitis), in which the ESR was relatively unchanged in a small sample of patients. By the time clinical activity became severe, however, patients in all disease categories manifested similarly high ESRs, with the exception of ulcerative proctitis in which the ESR remained low in the single patient tested.(ABSTRACT TRUNCATED AT 250 WORDS)