Granulomatous Enterocolitis Research Articles

Granulomatous Colitis Due to Hermansky-Pudlak Syndrome

ABSTRACT Hermansky-Pudlak syndrome (HPS) is a rare genetic disorder characterized by oculocutaneous albinism, bleeding diathesis, and multiorgan involvement. Granulomatous enterocolitis may occur in a subset of patients. Distinguishing HPS from other diseases such as Crohn's disease can be challenging, and managing HPS-associated colitis is complex. Recent reports suggest potential efficacy of infliximab in treating HPS-related granulomatous colitis. Here, we document the case of a 27-year-old patient with genetically confirmed HPS type 1, presenting with granulomatous colitis and successfully treated with corticosteroids and infliximab.

Pathological and Microbiological Findings in Fatal Cases of Salmonellosis in Captive Bothrops Snakes in Southern Brazil

Salmonella spp. are gram-negative commensal bacteria of vertebrates, including reptiles. Infected snakes may be asymptomatic or manifest clinical disease and death, especially after stressful events. Salmonellosis was diagnosed in 10 captive snakes from the Bothrops genus. The most frequent changes were emaciation (8/10), fibrinonecrotic or granulomatous hepatitis (8/9), fibrinonecrotic or granulomatous enterocolitis (8/9), necrotic and heterophilic myocarditis (2/10), fibrinonecrotic or granulomatous pancreatitis (2/5), fibrinoheterophilic osteomyelitis (1/10), fibrinous and pyogranulomatous pericarditis (1/10) and granulomatous splenitis (1/6). Salmonella enterica was isolated from six cases. The subspecies identified were arizonae (3/6), diarizonae (1/6) and houtenae (1/6), in addition to the serotype Typhimurium (1/6). In cases without isolation, there was immunolabelling of Salmonella spp. in intestinal (3/4), hepatic (1/4) and cardiac (1/4) lesions.

P360 Aggressive Inflammatory Bowel Disease is associated to Hermansky-Pudlak Syndrome: Characterization of a Puerto Rican Cohort

Abstract Background Hermansky-Pudlak Syndrome (HPS), a rare autosomal recessive disorder, is the most common single-gene disorder in Puerto Rico. It is characterized by an aberrant biogenesis of lysosome-related organelles inducing oculocutaneous albinism, bleeding diathesis, and damage to other organs. Around 30% of patients with HPS develop granulomatous enterocolitis, a Crohn’s-like inflammatory bowel disease (IBD). The mutant HPS1 gene is associated with a more severe Early Onset IBD (EO-IBD). We wish to describe a group of patients with HPS-associated IBD. Methods Puerto Ricans with HPS and concomitant IBD were recruited in our IBD clinic for a prospective cohort study. After informed consent, demographic and medical data were collected from the patient and the medical record. Variables included sex, HPS genotype, age at the time of IBD diagnosis, IBD location and behavior according to Montreal and Paris Classification, surgical interventions, medications, and extra-intestinal manifestations (EIM). Descriptive analysis was performed calculating mean and standard deviations. This study is approved by the MSC IRB. Results 13 patients with HPS and IBD, 9 with confirmed genotype 1, were identified: 8 males and 5 females. The mean age at the time of IBD diagnosis was 22 ± 11 years. 6 were diagnosed at ≤ 16 y/o (A1), 6 were diagnosed between 17-40 years (A2) and 1 patient was in the range of EO-IBD (7 y/o). 9 patients had advanced penetrating behavior (B3) of which 7 had concomitant perianal involvement. Most patients (9) had a surgical intervention; 8 have an ostomy. The majority (10) are using biologics (4 with concurrent immunomodulators). The most frequent EIM was peripheral arthropathy seen in 45%. Conclusion HPS patients had a severe course of IBD, as shown by age at diagnosis, phenotype, the prevalence of perianal disease, surgery and use of biologics. In comparison to a database of 836 Puerto Ricans with non HPS Crohn’s Disease, those with HPS were more likely to have surgeries (69% vs 55%, P=.303) and use biologics (77% vs 43%, P=.015). Gastrointestinal symptoms including bleeding may be overlooked by the primary physician. Proactive vigilance in patients with HPS to make an early diagnosis of IBD and aggressive medical treatment may result in better outcomes for these patients.

Oesophageal Obstruction in a Donkey Due to Mediastinal Lymphadenitis Caused by Mycobacterium avium Complex

Mycobacterial infections are rare in horses, donkeys and mules. Although there are a few reports in horses, mycobacterial disease is poorly documented in the donkey. Mycobacterial infection of equine species typically affects the alimentary tract, causing granulomatous enterocolitis resulting in diarrhoea and chronic weight loss, while lymph nodes and liver may also be affected. We now document recurrent oesophageal obstruction, secondary to cranial mediastinal lymphadenitis caused by Mycobacterium avium complex (MAC). To the best of our knowledge, this is the first report of MAC infection in a donkey in the UK.

S3215 Hermansky-Pudlak-Associated IBD: Is It the Same? Description of a Puerto Rican Cohort

INTRODUCTION: Hermansky-Pudlak Syndrome (HPS) is the most common single gene disorder in Puerto Rico. It is a rare autosomal recessive disorder due to aberrant biogenesis of lysosome-related organelles leading to oculocutaneous albinism, bleeding diathesis, and involvement in other organs. About 30% of patients with HPS develop a form of Crohn’s-like inflammatory bowel disease (IBD), granulomatous enterocolitis. Whether this is a manifestation of HPS or true IBD is still in debate. We wish to describe a group of patients with HPS-associated IBD. METHODS: This is a prospective cohort study in which phenotypically identified patients with HPS and concomitant IBD are recruited. After informed consent, a questionnaire with demographic and medical data is administered through patient interview and record review is performed. The variables collected are sex, HPS genotype, age at the time of IBD diagnosis, comorbidities, IBD location and behavior according to Montreal Classification, surgical interventions, medications, and extra-intestinal manifestations (EIM). This study is approved by the IRB. RESULTS: Ten patients with HPS and concomitant IBD were identified in our clinics - 5 males and 5 females. HPS genotype in 9 showed 8 were HPS-1 and 1 was HPS-3. The mean age at the time of IBD diagnosis was 22 ± 10 years. Six were diagnosed between ages 17 and 40 years and 4 patients were diagnosed at ≤16 y/o. Seven patients had colonic involvement, 3 had ileocolonic involvement. Sixty percent of patients had an advanced penetrating behavior and 50% had perianal involvement. Six patients had some type of surgical intervention. Three patients were on both a biologic and an immunomodulator (IMM), 5 were on a biologic alone, 1 on IMM alone, and 1 without maintenance treatment. The most frequent EIM was anemia in 40% of patients. CONCLUSION: HPS patients had a severe course of IBD, as shown by phenotype, surgery, and use of biologics. A younger age at diagnosis and a higher than usual prevalence of perianal disease also predict a complicated course. Further studies are necessary to determine if HPS-associated IBD is related to the genetic defect and if this may result in a different clinical course than idiopathic IBD.

Development of an outbred disease model of Hermansky-Pudlak Syndrome in Threespine Stickleback

Abstract Mounting evidence shows that humans respond heterogeneously to diseases and treatments due to their genetic variation, leading to the growth of the field of personalized medicine. Research on model organisms is vital to seek scientific understandings of disease in this broader context, but current research in nonhuman disease models struggles to demonstrate the genetic variability of humans. One disease that exemplifies this issue is Hermansky-Pudlak Syndrome (HPS). HPS is a genetic syndrome resulting from mutations in one of ten HPS genes involved in endosome trafficking, which can result in oculocutaneous albinism, blood diathesis, pulmonary fibrosis, vision impairment, and granulomatous enterocolitis phenotypically indistinguishable from Crohn’s Disease. Currently no disease models for HPS exist that accurately demonstrate the variability of the human disease. Here we present an outbred mutant model of threespine stickleback (Gasterosteus aculeatus) fish exhibiting symptoms consistent with HPS. Using genetic mapping approaches we narrowed this mutation to a region of the genome containing hps4the causative disease gene of Hermansky-Pudlak Syndrome Type 4. Using histological staining and imaging we are confirming the presence of each symptom comprising the syndrome and hope to develop the first outbred system to tackle this disease. Ultimately, the application of outbred medical models in diverse organisms will be important for the advancement of personalized medicine, greatly enhancing our understanding of how genetic variation affects disease states.

Milk yield and lactation stage are associated with positive results to ELISA for Mycobacterium avium subsp. paratuberculosis in dairy cows from Northern Antioquia, Colombia: a preliminary study.

Paratuberculosis is a slow-developing infectious disease characterized by chronic granulomatous enterocolitis. This disease has a variable incubation period from 6months to over 15years and is caused by Mycobacterium avium subsp. paratuberculosis (MAP). Some studies have been conducted in cattle during the last decades in Colombia. However, those studies were designed using relatively small populations and were not aimed to establish prevalence. This study aimed to determine the MAP seroprevalence in selected dairy herds and to explore risk factors associated with the serology results. Serum samples and related data were collected from 696 randomly selected bovines in 28 dairy herds located in 12 different districts in one of the main dairy municipalities in Colombia (San Pedro de los Milagros). The samples were analyzed using a commercial ELISA kit. The information on risk factors was analyzed using a logistic regression. The apparent seroprevalence was 3.6% (1/28) at the herd level and 2% (14/696) at the animal level. The number of days in milk production between 100 and 200days, and over 200days as well as the daily milk production between 20 and 40L/cow, and over 40L/cow were associated with MAP seropositivity with odds ratios of 4.42, 3.45, 2.53, and 20.38, respectively. This study demonstrates the MAP seroprevalence in dairy herds from Antioquia, Colombia and the possible relationship between MAP seropositivity, milk yield, and lactation stage.

Clinical Research Abstracts of the British Equine Veterinary Association Congress 2015.

Infiltrative disease of the intestine is an important cause of weight loss in the horse. Infiltration of inflammatory or neoplastic cells into the intestinal wall and intestinal fibrosis cause changes in the integrity of the intestinal wall. This may lead to altered intestinal permeability which can be measured using the contrast medium iohexol. To determine if iohexol intestinal permeability, as evaluated by serum iohexol concentration, could be used to differentiate between healthy horses and horses with infiltrative disease of the large colon. Prospective non-randomised controlled clinical trial. Six healthy adult horses and 4 horses with chronic infiltrative disease of the large colon were used in the study. Infiltrative disease was confirmed on post mortem in all cases, and included alimentary lymphoma and mycobacterial granulomatous enterocolitis. Following a 16-h fast, each horse was dosed with 1.0 ml/kg bwt of iohexol as a 10% solution via nasogastric intubation. Blood samples were collected at 0, 30, 60, 120, 180, 240, 300, 360, 420 and 480 min after dosing. Iohexol concentration was determined using HPLC-UV and the differences between the groups were analysed with a repeated measures ANOVA. There was a statistically significant difference in iohexol serum concentration between the diseased and nondiseased horses (P = 0.001). The overall difference in the mean iohexol concentration between the 2 groups was 6.07 (95% CI 3.19-8.96) μg/ml, however there appeared to be a trend towards increasing difference at later time points (240, 300, 360 min). The iohexol permeability test has potential as a diagnostic tool for estimation of intestinal permeability in horses with infiltrative intestinal disease. Further studies are warranted to determine whether the test can be used to determine the site of intestinal pathology, predict the prognosis and potentially evaluate the response to treatment. The authors thank Professor Riitta-Mari Tulamo and Professor Thomas Spillmann and the staff of Equine College Ypäjä and the University of Helsinki Equine Teaching Hospital. The cooperation of horse owners is gratefully acknowledged. Ethical animal research: The study protocol was approved by the National Animal Experiment Board of Finland (Eläinkoelautakunta ELLA, Request for Animal Experiments, ref. no. ESAVI-2010-06567/Ym-23). For client-owned animals, owner informed consent was obtained. This study was funded by the Faculty of Veterinary Medicine, University of Helsinki, Finland. Competing interests: None declared.

The Great Mimicker: Abdominal Tuberculosis and Small Bowel Obstruction in an Immunocompetent Adult

Purpose: An 80-year-old female Filipino patient presented with vomiting, right upper quadrant abdominal pain, and constipation for three days. She noted poor oral intake, significant weight loss, and night sweats for one year. The patient was cachectic. Abdomen was mildly-tender and distended. CT abdomen showed bowel wall thickening and obstruction at the level of the ileocecal valve. Colonoscopy showed a nearly obstructing mass in the ascending colon. Biopsy showed granulation tissue formation, and was negative for malignancy. Given the persistent obstruction, right hemicolectomy was performed. Pathology showed granulomatous enterocolitis, appendicitis, and lymphangitis with mucosal ulceration. Interferon-gamma release assay was positive; however, acid fast stain and TB PCR were negative. There are international case reports and small case studies discussing the diagnostic workup for abdominal TB. Patients present with symptoms similar to our patient. They will commonly have normal chest radiographs, and acid fast staining of the sputum is often negative, as there may not be concurrent pulmonary involvement. Endoscopy shows right sided nodules, polyps, strictures, ulcers, or masses. A majority of lesions will heal completely with treatment. Biopsies show granulomas, but AFB and culture are frequently negative. PCR has 58-79% sensitivity and 68-100% specificity. Diagnosis is confirmed by response to treatment. Abdominal TB does not have a gold standard for diagnosis, and therefore, the clinician must have a high index of suspicion, especially in the United States, where this presentation for TB is rare in an immunocompetent adult.FigureFigure

Ocorrência de paratuberculose em búfalos (Bubalus bubalis) em Pernambuco

A paratuberculose (doença de Johne) é uma das doenças de maior importância econômica para ruminantes em vários países e pode representar uma ameaça ao desenvolvimento da pecuária brasileira. É uma doença infecto-contagiosa que provoca enterocolite granulomatosa crônica, incurável e de difícil controle, cujo agente é o Mycobacterium avium subsp. paratuberculosis (MAP). Descreve-se a ocorrência de paratuberculose em um rebanho de búfalos no Estado de Pernambuco, Brasil. Não foi encontrado registro, na literatura, da ocorrência de paratuberculose em búfalos no país. De 100 búfalos, cinco mostravam sinais clínicos característicos da doença. À necropsia de dois animais as lesões estavam restritas ao intestino delgado com evidente espessamento da mucosa, aumento de linfonodos mesentéricos e vasos linfáticos proeminentes e dilatados. À microscopia, observaram-se na mucosa do intestino, infiltrado inflamatório granulomatoso com numerosos macrófagos epitelióides e células gigantes de Langhans, além de bacilos álcool-ácido resistentes (BAAR) visualizados através da coloração de Ziehl-Neelsen (ZN). Nos linfonodos mesentéricos, havia espessamento da cápsula e marcada inflamação granulomatosa. O exame direto pela técnica de ZN para pesquisa do bacilo em esfregaços de fezes, raspado de mucosa intestinal e imprint de linfonodos mesentéricos resultou positivo. A PCR IS900 específico de linfonodo mesentérico e mucosa intestinal revelou amplificação de um fragmento de aproximadamente 110pb, confirmada pela comparação com outras sequências de M. avium subsp. paratuberculosis disponíveis no GenBank.

Genetic dissection of granulomatous enterocolitis and arthritis in the intramural peptidoglycan-polysaccharide-treated rat model of IBD

Inflammatory arthropathies are common extraintestinal manifestations of inflammatory bowel diseases (IBD). As genetic susceptibility plays an important role in the etiology of IBD, we questioned how granulomatous enterocolitis and arthritis are genetically controlled in an experimental animal model displaying both conditions. Chronic intestinal and systemic inflammation was induced by intramural injection of peptidoglycan-polysaccharide (PG-PS) polymers in the ileocecal region of female F2 progeny derived from susceptible LEW and resistant F344 rats. Animals were followed for 24 days after injection and phenotyped by evaluating gross gut lesions, liver weight and granulomas, hematocrit, white blood cell count, and change in rear ankle joint diameters. Coinheritance of the phenotypic parameters with polymorphic DNA markers was analyzed by genome-wide quantitative trait locus (QTL) analysis. Linkage analysis revealed significant QTLs for enterocolitis and/or related phenotypes (liver granulomas, white blood cell count) on chromosomes 8 and 17. The QTL on chromosome 8 also showed suggestive linkage to arthritis. Significant QTLs for arthritis were detected on chromosomes 10, 13, 15, and 17. Analyses of the modes of inheritance showed arthritogenic contributions by both parental genomes. In addition, several other loci with suggestive evidence for linkage to 1 or several phenotypes were found. Susceptibility to PG-PS-induced chronic intestinal and systemic inflammation in rats is under complex multigenic control in which the genetic loci regulating arthritis are largely different from those controlling enterocolitis. Possible candidate genes within these QTL (including Tnfrsf11a/RANK, Gpc5, Il2ra, and Nfrkb) are also implicated in the respective human diseases.

Genetic dissection of granulomatous enterocolitis and arthritis in the intramural peptidoglycan-polysaccharide-treated rat model of IBD:

Genetic dissection of granulomatous enterocolitis and arthritis in the intramural peptidoglycan-polysaccharide-treated rat model of IBD:

An Unusual Presentation of Strongyloides stercoralis Infestation

An Unusual Presentation of Strongyloides stercoralis Infestation

Map Lesions: In Situ Investigation on Samples of Multibacillar and Paucibacillar Ovine PTBC

Paratuberculosis (PTBC) is a chronic inflammation of the intestines of ruminants but it can also strike other species, including primates. Ovine paratuberculosis lesions have been the subject of authoritative observations (Perez et al ., 1996). The macroscopic picture shows a thickening and wrinkling of the intestinal mucous membrane , regional lymphangitis and lymphandenopathy, principally found in the terminal part of the ileum but also in the colon, jejunum and duodenum. Histomorphological pictures are characterised by chronic granulomatous enterocolitis, whose typical clinical symptom is the loss of weight due to profuse diarrhea. The etiological agent of PTBC is the bacterium Mycobacterium avium subsp. paratuberculosis (MAP) (Marek, 1910); its presence gives rise to a persistent infection of the intestinal macrophages which appear foamy, in a small granuloma within the interfollicular-basal area of the Peyer’s plaques of the ileal tract. In some cases, even in the presence of marked lesions and clear, clinical symptomatology, coloration of the Ziehl-Nielsen (ZN) produces a negative result. DNA analysis of MAP has identified a peculiar insertion sequence, IS900, present in 15–20 pairs per genome (Green et al ., 1989).

Granulomatous Enterocolitis Associated with Hermansky-Pudlak Syndrome

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder. It consists of a triad of tyrosinase-positive oculocutaneous albinism (Ty-pos OCA), bleeding diathesis resulting from platelet dysfunction, and systemic complications associated with accumulation of ceroid lipofuscin. Many patients are from a small area in northwestern Puerto Rico. HPS has been associated with granulomatous enterocolitis in up to 20% of affected patients. It is not known whether this granulomatous colitis is a part of the syndrome, or represents an independent but associated process, such as Crohn's disease. This colitis can be severe, and has been reported to be poorly responsive to medical therapies including sulfasalazine, mesalamine, steroids, and metronidazole. We report a series of four patients with refractory enterocolitis in the setting of HPS who were treated at Mount Sinai Hospital between 1998 and 2005. A trial of infliximab was attempted in all four, and produced a complete response in two. Many phenotypic and pathologic similarities exist between granulomatous enterocolitis in HPS and Crohn's disease. However, it is unclear whether the granulomatous enterocolitis in HPS is because of ceroid deposition or reflects the coexistence of Crohn's disease and HPS. The occurrence of ileal involvement and perianal fistulization in our cases suggests that in at least some instances, HPS and Crohn's disease are truly associated.

This Month in Gastroenterology

This Month in Gastroenterology

Case of eosinophilic granulomatous enterocolitis caused by Strongyloides stercoralis infection with marked hypoalbuminemia and ascites

We report a 10‐year‐old boy presenting with generalized pitting edema, ascites, abdominal pain, and chronic mucous diarrhea for 4 weeks. He had underlying diseases of hemoglobin E and juvenile rheumatoid arthritis and had been treated with immunosuppressive agents for a long period of time, including prednisolone and methotrexate. After extensive investigations, Strongyloides stercoralis infection, leading to protein‐losing enteropathy and eosinophilic granulomatous enterocolitis, was diagnosed. In the present report, we demonstrate early colonoscopic findings, revealing patchy erythema and small raised mucosal nodules with erosions at the cecum. Histopathological study showed open ulceration with cryptitis, intense infiltration of eosinophils and histiocytes with granuloma formation, in which Strongyloides stercoralis larvae were noted.

IGF-I and TGF-beta1 have distinct effects on phenotype and proliferation of intestinal fibroblasts.

Insulin-like growth factor I (IGF-I) and transforming growth factor-beta1 (TGF-beta1) are upregulated in myofibroblasts at sites of fibrosis in experimental enterocolitis and in Crohn's disease (CD). We compared the sites of expression of IGF-I and TGF-beta1 in a rat peptidoglycan-polysaccharide (PG-PS) model of chronic granulomatous enterocolitis and fibrosis. We used the human colonic CCD-18Co fibroblast/myofibroblast cell line to test the hypothesis that TGF-beta1 and IGF-I interact to regulate proliferation, collagen synthesis, and activated phenotype typified by expression of alpha-smooth muscle actin and organization into stress fibers. IGF-I potently stimulated while TGF-beta1 inhibited basal DNA synthesis. TGF-beta1 and IGF-I each had similar but not additive effects to induce type I collagen. TGF-beta1 but not IGF-I potently stimulated expression of alpha-smooth muscle actin and stress fiber formation. IGF-I in combination with TGF-beta1 attenuated stress fiber formation without reducing alpha-smooth muscle actin expression. Stress fibers were not a prerequisite for increased collagen synthesis. TGF-beta1 upregulated IGF-I mRNA, which led us to examine the effects of IGF-I in cells previously activated by TGF-beta1 pretreatment. IGF-I potently stimulated proliferation of TGF-beta1-activated myofibroblasts without reversing activated fibrogenic phenotype. We conclude that TGF-beta1 and IGF-I both stimulate type I collagen synthesis but have differential effects on activated phenotype and proliferation. We propose that during intestinal inflammation, regulation of activated phenotype and proliferation may require sequential actions of TGF-beta1 and IGF-I, but they may act in concert to increase collagen deposition.

Bacterial cell wall polymers promote intestinal fibrosis by direct stimulation of myofibroblasts.

Normal luminal bacteria and bacterial cell wall polymers are implicated in the pathogenesis of chronic intestinal inflammation. To determine the direct involvement of bacteria and their products on intestinal fibrogenesis, the effects of purified bacterial cell wall polymers on collagen and cytokine synthesis were evaluated in intestinal myofibroblast cultures established from normal fetal and chronically inflamed cecal tissues. In this study, the intestines of Lewis rats were intramurally injected with peptidoglycan-polysaccharide polymers. Collagen and transforming growth factor (TGF)-beta1 mRNA levels were measured and correlated with mesenchymal cell accumulation by immunohistochemistry. The direct effects of cell wall polymers on fibrogenic cytokine and collagen alpha1 (type I) expression were evaluated in intestinal myofibroblast cultures. We found that intramural injections of bacterial cell wall polymers induced chronic granulomatous enterocolitis with markedly increased collagen synthesis and concomitant increased TGF-beta1 and interleukin (IL)-6 expression. Intestinal myofibroblast cultures were established, which both phenotypically and functionally resemble the mesenchymal cells that are involved in fibrosis in vivo. Bacterial cell wall polymers directly stimulated collagen alpha1 (I), TGF-beta1, IL-1beta, and IL-6 mRNA expression in the intestinal myofibroblasts derived from both normal and inflamed cecum. Neutralization of endogenous TGF-beta1 inhibited in vitro collagen gene expression. From our results, we conclude that increased exposure to luminal bacterial products can directly activate intestinal mesenchymal cells, which accumulate in areas of chronic intestinal inflammation, thus stimulating intestinal fibrosis in genetically susceptible hosts.

Interleukin 10 suppresses experimental chronic, granulomatous inflammation induced by bacterial cell wall polymers.

Interleukin 10 (IL10) inhibits monocyte/macrophage and T lymphocyte effector functions. This study examined the effect of systemically administered IL10 on acute and chronic granulomatous enterocolitis, hepatitis, and arthritis in a rat model. Lewis rats were injected intramurally with streptococcal peptidoglycan-polysaccharide (PG-APS) polymers. Beginning 12 hours before PG-APS injection, rats were treated daily with subcutaneous murine recombinant IL10 or vehicle for three or 17 days. IL10 attenuated acute enterocolitis in a dose dependent fashion (p < 0.01). Protective effects were more profound in the chronic granulomatous phase with decreased enterocolitis and markedly inhibited leucocytosis, hepatic granulomas, and chronic erosive arthritis (p < 0.001). IL10 downregulated tissue IL1, IL6, tumour necrosis factor alpha, and interferon gamma gene expression, consistent with the in vitro effects of IL10 on PG-APS-stimulated splenocytes. Caecal IL1 protein concentrations and IL2 and interferon gamma secretion by in vitro stimulated mesenteric lymph nodes were downregulated in IL10 treated animals. These results indicate that exogenous IL10 can inhibit experimental granulomatous inflammatory responses and suggest that IL10 treatment could be an effective new therapeutic approach in human disorders such as Crohn's disease, rheumatoid arthritis, and sarcoidosis.