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See detailEffects of Dexamethasone on the Profile of Cytokine Secretion in Human Whole Blood Cell Cultures
Franchimont, Denis; Louis, Edouard ULg; Dewé, Walthère ULg et al

in Regulatory Peptides (1998), 73(1), 59-65

EXPERIMENTAL OBJECTIVES: The interaction between the endocrine and immune systems is a very intriguing area. Endogenous glucocorticoids, as end-effectors of the hypothalamo-pituitary-adrenal axis, inhibit ... [more ▼]

EXPERIMENTAL OBJECTIVES: The interaction between the endocrine and immune systems is a very intriguing area. Endogenous glucocorticoids, as end-effectors of the hypothalamo-pituitary-adrenal axis, inhibit the immune and inflammatory responses and are used as immunosuppressive drugs in many inflammatory, autoimmune and allergic diseases. The aims of this study were to investigate the effects of dexamethasone on the profile of cytokine secretion in whole blood cell cultures from healthy subjects and to analyse the gender-related sensitivity to dexamethasone on each cytokine secretion. RESULTS: There was a significant inhibition by dexamethasone (from 1 to 100 nM) on the secretion of monokines (IL-1beta, IL-6, IL-8 and TNF alpha) and lymphokines (IL-2, IL-4, IL-10 and IFN gamma), either after LPS or PHA stimulation (P < 0.01). Interleukin 4 and IL-10 were less inhibited than IFN gamma (P < 0.05 at 1 nM, P < 0.01 at 10 nM and P < 0.001 from 100 nM to 10 microM). No gender difference was observed in the rate of inhibition of the secretion of each cytokine. CONCLUSION: This study shows that the inhibition of cytokine secretion by dexamethasone is more marked on Th1-type cytokines than on Th2-type cytokines. These data support the idea that glucocorticoids may induce a shift from the Th1 to Th2 profile of cytokine secretion. [less ▲]

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See detailCorticosteroid Treatment in Active Crohn's Disease
Belaiche, Jacques ULg; Louis, Edouard ULg

in Acta Gastro-Enterologica Belgica (1998), 61(2, Apr-Jun), 153-7

Despite recent improvements in the management of Crohn's disease, steroids are still the most efficacious treatment in flare ups of the disease. However they have significant side effects and are only ... [more ▼]

Despite recent improvements in the management of Crohn's disease, steroids are still the most efficacious treatment in flare ups of the disease. However they have significant side effects and are only effective in the short term. There is no consensus regarding initial dose or duration of corticotherapy. With 1 mg/Kg a day of oral prednisolone given for 3 to 7 weeks, 92% of the patients achieve clinical remission. Topical acting oral corticosteroids such as budesonide seem to represent an important therapeutic advance due to their better tolerance. The promising results of budesonide in mild and moderate flare ups need to be confirmed and its indication in severe disease beside high dose prednisolone has to be clarified. [less ▲]

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See detailNouveaux traitements immunomodulateurs dans la maladie de Crohn
Louis, Edouard ULg; Belaiche, Jacques ULg

in Médecine et Hygiène (1998), 56

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See detailTumour necrosis factor (TNF) gene polymorphism influences TNF-alpha production in lipopolysaccharide (LPS)-stimulated whole blood cell culture in healthy humans.
Louis, Edouard ULg; Franchimont, D.; Piron, Anne ULg et al

in Clinical & Experimental Immunology (1998), 113(3), 401-406

TNF-alpha is involved in infectious and immuno-inflammatory diseases. Different individuals may have different capacities for TNF-alpha production. This might determine a predisposition to develop some ... [more ▼]

TNF-alpha is involved in infectious and immuno-inflammatory diseases. Different individuals may have different capacities for TNF-alpha production. This might determine a predisposition to develop some complications or phenotypes of these diseases. The aims of our study were to assess the inter-individual variability of TNF-alpha production and to correlate this variability to a single base pair polymorphism located at position -308 in TNF gene. We studied 62 healthy individuals. TNF-alpha production after LPS stimulation was evaluated using a whole blood cell culture model. The TNF gene polymorphism was studied by an allele-specific polymerase chain reaction. Other cytokines produced in the culture, soluble CD14 concentrations and expression of CD14 on blood cells were also measured. Among the 62 individuals, 57 were successfully genotyped. There were 41 TNF1 homozygotes and 16 TNF1/TNF2 heterozygotes. TNF-alpha production after LPS stimulation of whole blood cell culture was higher among TNF2 carriers than among TNFI homozygotes (929pg/ml (480-1473pg/ml) versus 521 pg/ ml (178-1307 pg/ml); P<0.05). This difference was even more significant after correction of TNF-alpha production for CD14 expression on blood cells. In conclusion, the single base pair polymorphism at position -308 in the TNF gene may influence TNF-alpha production in healthy individuals. [less ▲]

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See detailLes récidives post-opératoires de la maladie de Crohn
Belaiche, Jacques ULg; Louis, Edouard ULg

in Lemann, M.; Modigliani, R. (Eds.) Les maladies inflammatoires intestinales (1998)

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See detailIncidence of Inflammatory Bowel Disease in the Area of Liege: A 3 Years Prospective Study (1993-1996)
Latour, Pascale ULg; Louis, Edouard ULg; Belaiche, Jacques ULg

in Acta Gastro-Enterologica Belgica (1998), 61(4, Oct-Dec), 410-3

A first prospective epidemiological study of IBD was conducted in the area of Liege. The duration of the study was short taking into account the small size of the population (1 million inhabitants ... [more ▼]

A first prospective epidemiological study of IBD was conducted in the area of Liege. The duration of the study was short taking into account the small size of the population (1 million inhabitants). Therefore we carried out a 3 years prospective study. METHOD: Private and public gastroenterologists completed a questionnaire for each new case they diagnosed between 01.06.1993 and 31.05.1996. RESULTS: During that period 270 IBD patients were identified: 137 (51%) had Crohn's disease (CD), 111 (41%) had ulcerative colitis (UC) including 32 proctitis (29% of UC) and 22 (8%) had unclassified colitis. The mean annual incidence per 10(5) was 4.5 for CD and 3.6 for UC. The female/male ratio was 1,6 for CD and 0,5 for UC. The median age at the time of diagnosis was 30 years for CD and 39 years for UC. The mean time between the onset of symptoms and the diagnosis was 6,5 months for CD and only 4,8 months for UC. Family history of IBD was found in 15% of patients with CD and in 7% of UC. CONCLUSIONS: These data show a high incidence of IBD in the area of Liege. These results confirm those reported during the first year of the prospective study which were similar to those observed in North-western France. Contrary to the other countries of Northern Europe, the incidence of UC is lower than the one of CD. Belgium appears to be a privileged country to undertake a national register and to study epidemiological aspects of IBD. [less ▲]

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See detailA High Serum Concentration of Interleukin-6 Is Predictive of Relapse in Quiescent Crohn's Disease
Louis, Edouard ULg; Belaiche, Jacques ULg; Van Kemseke, Catherine ULg et al

in European Journal of Gastroenterology & Hepatology (1997), 9(10), 939-44

BACKGROUND/AIMS: Relapses of Crohn's disease are difficult to predict. We assessed the value of serum level of interleukin-6, tumour necrosis factor alpha (TNF-alpha) and soluble TNF receptors as ... [more ▼]

BACKGROUND/AIMS: Relapses of Crohn's disease are difficult to predict. We assessed the value of serum level of interleukin-6, tumour necrosis factor alpha (TNF-alpha) and soluble TNF receptors as predictors of relapse in quiescent Crohn's disease. PATIENTS/METHODS: Thirty-six patients with inactive Crohn's disease, treated or not, were included. Various clinical and biological parameters, including interleukin-6, TNF-alpha and soluble TNF receptors serum levels were measured at inclusion in the study and the patients were followed clinically for 1 year. The relapse was defined as a Crohn's Disease Activity Index (CDAI) greater than 150 with an increase greater than 100 compared to the inclusion value. We analysed the ability of these parameters to predict relapse in parallel to clinical characteristics and other laboratory parameters. RESULTS: Among the 32 variables tested, interleukin-6 serum level had the greatest ability to predict the time-to-relapse, with 17-fold chance of relapse over a 1-year period for patients with an interleukin-6 serum level greater than 20 pg/ml than for patients with a lower level (P < 0.001). A high serum level of the soluble TNF receptors p55 and p75 also had significant predictive value, in contrast to TNF-alpha serum levels. An interleukin-6 serum level greater than 20 pg/ml and either an acid alpha-1-glycoprotein level greater than 1.1 g/l or a soluble interleukin-2 receptor serum level greater than 95 pM/l were risk factors selected by a stepwise multivariate analysis. In both models a good prognosis group was defined by the absence of the two risk factors, a bad prognostic group by the presence of the two risk factors and an intermediate in between. With both models, the good prognosis group included 17 patients who experienced no relapse over the 1-year follow-up, whereas all patients (seven with the first model and six with the second) in the bad prognosis group had a relapse during the follow-up. Looking specifically at two homogeneous subgroups including either naturally/5-aminosalicylic acid (5-ASA) quiescent or corticoid quiescent patients, a very good predictive value for interleukin-6 serum concentration was also found. CONCLUSION: Interleukin-6 serum level alone or in association with other biological parameters such as acid alpha-1-glycoprotein or the soluble interleukin-2 receptor serum level may be useful for predicting the course of the disease in patients with quiescent Crohn's disease. [less ▲]

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See detailGenetic markers may predict disease behavior in patients with ulcerative colitis.
Roussomoustakaki, M.; Satsangi, J.; Welsh, K. et al

in Gastroenterology (1997), 112(6), 1845-53

BACKGROUND & AIMS: Recent studies have suggested that HLA DRB1*0103 and allele 2 of the interleukin 1 receptor antagonist (IL-1RA) gene predict severe and extensive ulcerative colitis, respectively. The ... [more ▼]

BACKGROUND & AIMS: Recent studies have suggested that HLA DRB1*0103 and allele 2 of the interleukin 1 receptor antagonist (IL-1RA) gene predict severe and extensive ulcerative colitis, respectively. The aim of this study was to test these hypotheses in patients undergoing surgery for their colitis. METHODS: HLA DRB1 and DQB1 genotyping was performed in 99 patients and 472 controls. Genotyping for polymorphisms of genes encoding tumor necrosis factor alpha and IL-1RA was performed in 107 patients and 89 controls. Measurement of antineutrophil cytoplasmic antibody (ANCA) was performed in 72 patients and 58 healthy subjects by fixed neutrophil enzyme-linked immunosorbent assay and indirect immunofluorescence. RESULTS: The DRB1*0103 allele was increased in patients (14.1% vs. 3.2% in controls; P < 1 x 10[-5]). This association was greatest in patients with extensive disease (15.8%; P < 0.0001) or extraintestinal manifestations (22.8%; P < 0.0001): mouth ulcers (25.8%; P < 0.0001), arthritis (27.2%; P < 0.0001), and uveitis (35.7%; P < 0.0001). The DRB1*04 alleles were reduced in patients (P = 0.005). Differences were noted between extensive and distal disease in the frequency of allele 2 of IL-1RA (10.9% in distal vs. 28.6% in extensive; P = 0.01) and allele 2 homozygosity. ANCA was detected in 76.4% of patients. Carriage of IL-1RA allele 2 and tumor necrosis factor 2 allele was increased in ANCA-positive patients. CONCLUSIONS: Genetic markers may predict disease behavior in ulcerative colitis. [less ▲]

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See detailExtensive Ulcerative Colitis and Extraintestinal Manifestations in a Patient with Hiv Infection and Significant Cd4 T-Cell Lymphopenia
Louis, Edouard ULg; Moutschen, Michel ULg; de Marneffe, Pierre et al

in Gastroentérologie Clinique et Biologique (1997), 21(11), 884-7

We report a heterosexual patient with HIV infection and a CD4 T-cell count of 0.45 x 10(9)/L who developed mild ulcerative proctitis, sacroileitis and oligoarthiritis. While he was treated with 5 ... [more ▼]

We report a heterosexual patient with HIV infection and a CD4 T-cell count of 0.45 x 10(9)/L who developed mild ulcerative proctitis, sacroileitis and oligoarthiritis. While he was treated with 5-aminosalicylic enemas, the patient rapidly developed severe pancolitis. An emergency colectomy without procetectomy was performed. A few months later, he suffered recurrence of ulcerative proctitis, aggravation of arthritic pain and developed anterior uveitis. All symptoms disappeared after proctectomy. There was no evidence for opportunistic infection or Kaposi's sarcoma. Antineutrophil cytoplasmic antibodies were positive and the HLA-B27 antigen was present. CD4 counts were lower during the phases of active disease than during remission. This case demonstrates that severe ulcerative colitis can occur in the presence of moderate T-cell defects. In view of a recent report of remission of Crohn's disease under comparable circumstances, it is possible that the extent of T-cell involvement in both diseases is radically different. [less ▲]

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See detailLe traitement corticoïde dans les poussées de la maladie de Crohn de l'adulte
Belaiche, Jacques ULg; Louis, Edouard ULg

in Médecine et Hygiène (1997), 55

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See detailFamilial Crohn's Disease: A Study of 18 Families
Franchimont, D.; Belaiche, Jacques ULg; Louis, Edouard ULg et al

in Acta Gastro-Enterologica Belgica (1997), 60(2, Apr-Jun), 134-7

The high frequency of familial Crohn's disease (CD) suggests a genetic predisposition. The most recent data from epidemiology and molecular biology are consistent with a multifactorial, polygenic ... [more ▼]

The high frequency of familial Crohn's disease (CD) suggests a genetic predisposition. The most recent data from epidemiology and molecular biology are consistent with a multifactorial, polygenic inheritance with a possible genetic heterogeneity. The aim of our study was, first to compare familial and sporadic CD on the basis of the type and location of the disease, and age at diagnosis, and second, to evaluate among families, the concordance rate for the type and location of the disease. PATIENTS AND METHODS: 18 families with 2 (n = 16) and 3 (n = 2) affected first degree relatives were studied. They were compared to a population of 154 sporadic CD coming from the same gastroenterology unit. RESULTS: Age at diagnosis was the same in sporadic and familial CD. There was an increased frequency of ileal (p = 0.02), and fibro stenotic (p = 0.005) CD and a decreased frequency of colonic (p = 0.006) and inflammatory (p = 0.02) disease, in familial CD. There was a significant increase in concordance rate for fibrostenotic disease (p < 0.001) and a decrease for inflammatory disease (p < 0.01), among the families. The observed concordance rate for the location of the disease was not significantly different from the expected one. In conclusion, these data suggest that CD may be heterogenous and that different clinical patterns may be determined either by genetic or environmental factors. [less ▲]

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See detailGenetics and Inflammatory Bowel Disease: From Association Studies to Wide Genome Screen
Louis, Edouard ULg; Belaiche, Jacques ULg

in Acta Gastro-Enterologica Belgica (1997), 60(3, Jul-Sep), 201-3

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See detailTwo stage genome-wide search in inflammatory bowel disease provides evidence for susceptibility loci on chromosomes 3, 7 and 12.
Satsangi, J.; Parkes, M.; Louis, Edouard ULg et al

in Nature Genetics (1996), 14(2), 199-202

Crohn's disease (CD) and ulcerative colitis (UC), the chronic inflammatory bowel diseases (CIBD), are common causes of gastro-intestinal disease in the Western world, with a combined prevalence of 100-200 ... [more ▼]

Crohn's disease (CD) and ulcerative colitis (UC), the chronic inflammatory bowel diseases (CIBD), are common causes of gastro-intestinal disease in the Western world, with a combined prevalence of 100-200/100,000 (ref. 1). Epidemiological studies, particularly concordance rates in twin pairs and siblings, strongly implicate genetic susceptibility in the pathogenesis of CIBD. In fact, the relative contribution of genetic factors to the pathogenesis of CD may be greater than in schizophrenia, asthma or hypertension, and at least equivalent to that in insulin-dependent diabetes. Systematic screening of the entire human genome now provides a strategy for the identification of susceptibility genes in complex polygenic disorders. We undertook a two-stage genome search for susceptibility genes in inflammatory bowel disease involving 186 affected sibling pairs from 160 nuclear families. We provide strong evidence for the presence of susceptibility loci for both CD and UC on chromosome 3, 7 and 12. We obtained the highest lod score (5.47; P = 2.66 x 10(-7) with the marker D12S83 and lod scores of 3.08 and 2.69 for D7S669 and D3S1573, respectively. Our data suggest that CD and UC are closely related, but distinct, polygenic disorders that share some, but not all, susceptibility genes. [less ▲]

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See detailIncidence of Inflammatory Bowel Disease in the Province of Liege (Belgium). La Societe De Gastroenterologie Liegeoise
Latour, Pascale ULg; Belaiche, Jacques ULg; Louis, Edouard ULg et al

in Acta Gastro-Enterologica Belgica (1996), 59(1, Jan-Mar), 3-6

Up to now, as there is no national registry of patients with inflammatory bowel disease (IBD) in Belgium, the study of IBD epidemiology in our country is only possible through institutional or regional ... [more ▼]

Up to now, as there is no national registry of patients with inflammatory bowel disease (IBD) in Belgium, the study of IBD epidemiology in our country is only possible through institutional or regional series. Therefore we conducted a prospective epidemiologic study of IBD in the Province of Liege (1 million inhabitants). METHODS: 29 (out of 47) private and public gastroenterologists completed a standard questionnaire for each patient consulting for the first time with clinical symptoms compatible with IBD between 1/06/1993 and 31/05/1994. RESULTS: During that period 104 cases of IBD were recorded: 56 (54%) Crohn's disease (CD), 36 (35%) ulcerative colitis (UC) including 7 proctitis (19% of UC) and 12 (11%) unclassified colitis. The annual incidence was 5.5 per 100.000 for CD and 3.5 for UC. The sex ratio F/M was 1.7 for CD and 0.7 for UC. The median age at the time of diagnosis was 33.5 yrs for CD and 40 yrs for UC. The highest age specific incidence rate for CD and UC was between 20 and 29 yrs : 13.6 and 6.1, respectively. CONCLUSIONS: This first Belgian prospective study has shown an incidence rate for CD comparable with that seen in north European studies but lower than that seen for UC. These results were similar to those observed in the northern part of France. Belgium appears to be a privileged country to undertake a national register and to study epidemiological aspects of IBD. [less ▲]

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See detailIntestinal Permeability in Crohn's Disease
Franchimont, D.; Louis, Edouard ULg; Simon, Sarah ULg et al

in Acta Gastro-Enterologica Belgica (1996), 59(1, Jan-Mar), 15-9

We summarize the anatomical and physiological basis and the ways of measuring the intestinal permeability. We review the studies of the intestinal permeability in Crohn's disease. We analyse the ... [more ▼]

We summarize the anatomical and physiological basis and the ways of measuring the intestinal permeability. We review the studies of the intestinal permeability in Crohn's disease. We analyse the involvement of an abnormal intestinal permeability in the pathogenesis of Crohn's disease, as a primary or secondary defect. We discuss the potential usefulness of the measure of intestinal permeability in Crohn's disease activity assessment, relapse prediction and efficacy of treatment. [less ▲]

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See detailCytokine gene polymorphisms in inflammatory bowel disease.
Louis, Edouard ULg; Satsangi, J.; Roussomoustakaki, M. et al

in Gut (1996), 39(5), 705-10

BACKGROUND: Concordance rates in siblings and twins provide strong evidence that genetic susceptibility is important in the pathogenesis of inflammatory bowel disease. The number and identity of ... [more ▼]

BACKGROUND: Concordance rates in siblings and twins provide strong evidence that genetic susceptibility is important in the pathogenesis of inflammatory bowel disease. The number and identity of susceptibility genes is largely uncertain. Cytokine genes are attractive candidate loci. AIMS: To study allelic frequencies of polymorphisms of the interleukin-1 receptor antagonist (IL-1RA) gene and the tumour necrosis factor alpha gene in patients with inflammatory bowel disease. SUBJECTS: One hundred and twenty nine North European caucasoid patients with ulcerative colitis, 120 patients with Crohn's disease, and 89 healthy controls. METHODS: Genotyping was performed by polymerase chain reaction. A variable number of tandem repeats (VNTR) in the IL-1RA gene and a single base pair polymorphism in the TNF alpha gene promoter region (TNF-308) were analysed. RESULTS: No significant differences in IL-1RA VNTR allelic frequencies were noted between Crohn's disease (allele 1: 72.6%, allele 2: 24.7%, allele 3: 2.6%), ulcerative colitis (72.6%, 24.3%, 3.1%, respectively), and controls (76.9%, 20.8% and 2.3%). Some 42.4% of patients with ulcerative colitis and 43.4% patients with Crohn's disease were carriers of allele 2, compared with 34.8% healthy subjects. The TNF2 allele was modestly reduced in Crohn's disease (13.2%), compared with healthy subjects (21.3%; p = 0.04), and ulcerative colitis (21.6%). CONCLUSIONS: The associations demonstrated are modest: these polymorphisms are unlikely to be important determinants of overall disease susceptibility. [less ▲]

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See detailUtilisation des antibiotiques dans la maladie de Crohn : de la théorie à la pratique
Louis, Edouard ULg; Drion, V.; Belaiche, Jacques ULg

in Médecine et Hygiène (1996), 54

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See detailDecrease in systemic tolerance to fed ovalbumin in indomethacin-treated mice.
Louis, Edouard ULg; Franchimont, D.; Deprez, Manuel ULg et al

in International Archives of Allergy & Immunology (1996), 109(1), 21-6

The oral administration of non-steroidal anti-inflammatory drugs (NSAID) to animals induces a quick increase in intestinal permeability and secondary inflammatory lesions of the intestine. The mechanisms ... [more ▼]

The oral administration of non-steroidal anti-inflammatory drugs (NSAID) to animals induces a quick increase in intestinal permeability and secondary inflammatory lesions of the intestine. The mechanisms leading to the inflammatory lesions are hypothetical. The increased intestinal permeability could allow a greater mucosal and systemic penetration of fed antigens and bacterial products leading to an abnormal mucosal and systemic immune and inflammatory response toward these materials. We examined the effect of oral dosing with indomethacin on ovalbumin serum levels and the systemic immune response to ovalbumin in mice fed with ovalbumin. The ovalbumin serum level was higher in indomethacin-treated mice and the increase was proportional to the dose of indomethacin. It was associated with epithelial and subepithelial lesions. Moreover, the systemic humoral and, to a lesser extent, the cellular tolerance were partially abrogated in the treated mice. These findings suggest that the oral administration of indomethacin in mice induces an increased passage of fed antigen through the intestinal epithelium associated with a decrease in systemic tolerance to this antigen. The reason for this decrease remains unclear. Besides a disequilibrium between systemic and mucosal immune responses, a loss of integrity of the intestinal epithelial cells and a direct immunomodulating effect of indomethacin may also be involved. This decrease in systemic tolerance to luminal antigen could be involved in the development of NSAID enteropathy. [less ▲]

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See detailSystemic Immune Response after Rectocolonic Administration of Ovalbumin in Mice
Louis, Edouard ULg; Franchimont, D.; Lamproye, Anne ULg et al

in International Archives of Allergy & Immunology (1995), 108(1), 19-23

The aim of our study was to determine the effect of a rectocolonic preimmunization with ovalbumin on the systemic immune response induced by a subsequent subcutaneous injection of this antigen in Balb/c ... [more ▼]

The aim of our study was to determine the effect of a rectocolonic preimmunization with ovalbumin on the systemic immune response induced by a subsequent subcutaneous injection of this antigen in Balb/c mice. One rectocolonic, but not intragastric, administration of 25 mg of ovalbumin induced a detectable increase in serum anti-ovalbumin antibody level. The level reached was however much lower than after subcutaneous injection. Both intragastric and rectocolonic immunization with ovalbumin induced specific systemic cellular tolerance. However, after rectocolonic, but not intragastric, preimmunization there was no systemic humoral tolerance to this antigen. These differences in systemic immune responses after rectocolonic or intragastric administration of ovalbumin could be due to different stimulation of the systemic immune system or to differences between the colonic and small bowel mucosal immune system, which remain to be elucidated. [less ▲]

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