La malaltia de Crohn és una malaltia inflamatòria intestinal de base immunitària. L’etiologia de la malaltia és desconeguda, encara que en general s’admet la següent definició: la malaltia és conseqüència d’una desregulació de la resposta immunitària en front als antígens comuns de la flora bacteriana intestinal en individus genèticament susceptibles. Un component important de la desregulació immunitària es la hiperactivació dels limfòcits T que es dóna en aquesta i altres malalties de tipus autoimmunitari, i en les que tradicionalment s’ha atribuït una major presència i producció de citocines per part de la població limfocitària Th1 en el teixit inflamat. Recentment, amb la descripció de la citocina IL-23 i la població Th17 se ha posat en dubte el paper principal de la població Th1 en les malalties inflamatòries de base immunitària. De fet, en algunes d’aquestes malalties s’ha descrit un augment de las cèl•lules Th17 així com de les citocines produïdes per aquesta població. L’objectiu d’aquesta tesi ha sigut caracteritzar el paper relatiu de les poblacions Th1 i Th17 en la mucosa intestinal inflamada i en la circulació perifèrica de pacients amb malaltia de Crohn activa o en remissió així com avaluar el paper i l’evolució d’aquestes poblacions limfocitàries en els estadis inicials (primers brots de la malaltia) i avançats de la malaltia. En aquest estudi observem que els períodes d’activitat inflamatòria en la malaltia de Crohn s’associen a una resposta sistèmica exacerbada de la població Th17, essent la producció de IL-17 en sobrenedant del cultiu de sang total, el percentatge de limfòcits CD4+IL-17+ i la producció de IL-17 per part d’aquestes cèl•lules més elevada que en els pacients amb malaltia inactiva i que en els controls sans. Paral•lelament hem descrit que la població Th1 circulant no presenta durant un brot d’activitat un augment tan generalitzat com la població Th17, sinó que només observem un augment en el percentatge de limfòcits CD4+IFN-γ+ circulants i en els dobles productors de IL-17 y IFN-γ. Els pacients que denominem debut (pateixen el primer brot de la malaltia) no presenten a nivell sistèmic un augment de la resposta Th17 ni Th1. A diferència del que observem en circulació perifèrica, en la mucosa intestinal inflamada trobem un augment dels trànscrits de les citocines característiques de la població Th17, tant en els pacients debut com en els que es troben en un estat més avançat de la malaltia. A més, en la mucosa inflamada d’ambdós grups de pacients trobem una major infiltració de cèl•lules IL-17+. A partir d’aquests resultats hipotetitzem un model per a la fisiopatologia de la malaltia de Crohn en el que la generació de limfòcits Th17 memòria podrien estar implicats en la cronicitat i recurrència de la malaltia. Així en les primeres fases de la malaltia només detectem un augment d’aquesta població en la mucosa intestinal, com seria d’esperar d’una resposta immunitària local. A conseqüència d’aquesta es generarà una població limfocitària de memòria immunitària que només detectem en circulació en aquells malalts que es troben ja en estadis més crònics de la malaltia. Amb aquesta hipòtesi podem explicar mitjançant mecanismes immunitaris diferents el fet que, en general, la malaltia de Crohn no es manifesta fins la segona o tercera dècada de vida d’un individu, mentre que un cop s’ha manifestat, la recurrència d’activitat inflamatòria és molt més freqüent (degut a la participació dels limfòcits memòria). / One component of the immune deregulation observed in Crohn’s disease is the massive infiltration of T lymphocytes in the inflamed tissue. Classically these hyperreactive lymphocytes have been attributed to the Th1 subpopulation. Recently the description of IL-23 cytokine and Th17 population has questioned the main role given to Th1 population. In this regard, an increase in the frequency of Th17 cells and in the production of their signature cytokines has been already described in some inflammatory diseases. In this study we have observed that active inflammation in Crohn’s disease associates to an increased systemic response of Th17 cells described as overproduction of IL-17 in supernatants of whole blood cultures, increased percentage of CD4+IL-17+ lymphocytes and increased production of IL-17 from these cells related to remission periods of disease or healthy controls. Early patients (patients who suffer their first flare of the disease) do not present a systemic increase of Th1 or Th17 cells despite suffering of active inflammation. Otherwise, in inflamed intestinal mucosa there is an increase in the expression of Th17 cytokines both in early as well as late chronic patients. Moreover we found a significant higher number of Th17 cells infiltrating the mucosa of both groups of patients. Taking these results into account we hypothesize a model for the physiopathology of Crohn’s disease in which the generation of memory Th17 lymphocytes could be involved in the chronicity and recurrence of the disease. Therefore, in early phases of disease we only detect an increase of this population in the intestinal mucosa, as we could expect from a local immune response. As a consequence of this activation there would be a generation of memory lymphocytes that we can detect in peripheral circulation only in that patients that have already suffered repeated flares of the disease. This hypothesis allows us to explain the different immune mechanisms that could be acting during the evolution of Crohn’s disease, as it is the first appearance of disease, generally occurring during the second or third decade of the individual life, and the subsequent appearance of recurrences that are much more frequent and life-long lasting.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2005. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Bakgrund: Crohns sjukdom och ulcerös kolit är två huvudtyper som utmärker inflammatorisk tarmsjukdom. Inflammatorisk tarmsjukdom påverkar mag- och tarmkanalen och har ett oförutsägbart sjukdomsförlopp. Inflammatorisk tarmsjukdom debuterar vanligtvis i åldern 15-30 och kan ge ogynnsamma konsekvenser i personens dagliga aktiviteter eftersom han eller hon är upptagen med att exempelvis studera, skapa karriär eller bilda familj. Sjukdomarna har flera gemensamma särdrag där de förekommer i så kallade skov med perioder med försämring då tarmslemhinnan blir inflammerad och sårig, vilket leder till symtom som exempelvis blodiga eller slemmiga diarréer, viktnedgång, buksmärtor och trötthet Syfte: Syftet med uppsatsen är att beskriva konsekvenser av att leva med Crohns sjukdom eller Ulcerös kolit hos vuxna personer. Metod: En litteraturöversikt. En litteratursökning gjordes som ledde till sex granskade artiklar. Resultatartiklarna analyserades sedan utifrån det valda syftet. Resultat: I analysen av resultatartiklarna framkom det fem olika återkommande teman. Dessa teman är fysiska konsekvenser av sjukdomen, psykiska konsekvenser av sjukdomen, sociala konsekvenser, förlust av kontroll samt påverkad föräldraroll. Flera teman innehöll subteman. Diskussion: Olika aspekter av patientens liv klarlades i resultatet vilket gör det möjligt för sjuksköterskan att i mötet med patienten kunna ge bra stöd och omsorg. Resultatet uppmärksammar de problem som patienten har i mötet med vårdpersonalen. Genom att upplysa och göra vården uppmärksam kring problemen så kan det underlättas för patienten i hans eller hennes behandling. Genom att lära patienten att hantera sin sjukdom och få behandling vid första tecken på återfall kan hans eller hennes lidande minska. / Background: Two main types that characterize inflammatory bowel disease are Crohn’s disease and ulcerative colitis. Inflammatory bowel disease affecting the digestive tract, and has an unpredictable disease course. Inflammatory bowel disease onset is usually between the ages of 15-30. It can cause adverse effects in a person’s daily activities because he or she is busy studying, building a career, raising a family and so on. Diseases have several common features. They occur in so-called relapses with periods of worsening when the gut lining becomes inflamed and ulcerated. It leads to symptoms such as bloody or slimy diarrhea, weight loss, abdominal pain and fatigue. Aim: The purpose of this paper is to describe the impact of living with Crohn's disease or ulcerative colitis in adults. Methods: A literature review. A literature search was performed which resulted in six peer-reviewed articles. Results Articles were then analyzed based on the selected object. Results: The analysis of the articles revealed five recurring themes. These themes are physical aspects of the disease, mental aspects of the disease, social aspects, and loss of control as well as being a parent whom are living with inflammatory bowel disease. Several themes also hold underlying themes. Discussions: Different aspects of the patients’ life were clarified in the results. It allowed the nurse to be prepared and provide god support and care when meeting with the patient.  The result highlights the problems that the patient has been in meetings with nursing staff. The attention on the problems in the patients’ treatment must be enlightened. By teaching patients to manage their condition and get treatment at the first sign of relapse, his or her suffering will decline.

Risk factors for psychological insult following deployment to Operation Enduring Freedom or Operation Iraqi Freedom among veterans: A systematic review: The systematic review aimed to establish more clearly the risk factors for mental health problems in the veteran population. Five databases were searched. Included studies (n = 10) required that veterans served in Operation Enduring Freedom (OEF) and/or Operation Iraqi Freedom (OIF) and included risk factors of mental health problems among the veteran population. Data from included studies were extracted and critically appraised based on critical appraisal tools following a narrative approach to synthesise data. All of the studies reviewed identified risk factors, although due to their heterogeneous nature key findings varied considerably. However, it was consistently reported that combat exposure and deployment experiences were associated with emergence of post operational mental health problems. The current review provides preliminary evidence that there are a number of specific risk factors that may increase susceptibility to mental health problems subsequent to military deployment. It is suggested that interventions are needed in order to mitigate risk factors and bolster protective factors. A cross-sectional study investigating the impact of disease activity and disease related cognitions on adjustment in Inflammatory Bowel Disease: The research journal aimed to investigate the degree to which psychological illness related cognitions will mediate the effect of disease activity on Quality of Life (QoL). In addition, to assess the impact of disease activity, and several psychological factors, in several adjustments outcomes in IBD to see whether the adjustment variables are significant predictors of multiple outcomes. Mediation was used followed by an exploratory cross-sectional correlational design. Three hundred and thirty eight participants were recruited through an IBD charity and invited to respond to a self-report questionnaire online. Measures targeted different aspects of the IBD profile to give an indication of adjustment associated with IBD diagnosis, psychological factors and Quality of Life (QoL). Mediation analysis found support for significant indirect effects on the relationship between disease activity and QoL through Gastrointestinal (GI) anxiety, perceived disability and illness representations. The subsidiary analysis indicated that pain catastrophising, disease activity, stigma, illness representations and GI anxiety were found to be significant predictors of adjustment in IBD. The results indicate that there is an important relationship with the adjustment factors, QoL, and psychological functioning. In addition, stress, depression, anxiety and QoL were found to be predicted by the adjustment factors. The current study has provided insight into psychological factors and adjustment indicators from a multi-faceted perspective, which will facilitate advancement of managing IBD from a biopsychosocial framework with a view to enable more effective disease management.

Fundamento e objetivo: Mudanças na ingestão de fibra e água podem influenciar a fisiologia intestinal. Este conceito simplista fundamenta a recomendação médica popular de aumentar o consumo de fibras e ingerir 2 litros de água por dia para o tratamento da constipação intestinal. O nosso objetivo foi avaliar o que há de verdadeiro nesta recomendação, primeiramente em indivíduos saudáveis. Métodos: Neste ensaio clínico randomizado, não cego, de grupos paralelos, 20 voluntários sadios tiveram suas variáveis basais determinadas (dieta, hábito intestinal, qualidade de vida e microbiota intestinal), seguido de randomização para tratamentos de 14 dias com aumento na ingestão de fibras (grupo F) ou aumento de fibras acompanhado da ingestão de 2 litros de água por dia (grupo FA), repetindo-se a aferição das variáveis ao final. Resultados: Dezenove participantes foram analisados, sendo 10 no grupo F e 9 no grupo FA. A maioria dos participantes (68,4%) desenvolveu um ou mais sintomas abdominais, particularmente os do grupo F, em comparação ao FA (90% vs. 44%; P = 0,034). Participantes de ambos os grupos aumentaram significativamente o número de evacuações/semana (grupo F: 6,8 antes vs. 8,8 depois; grupo FA: 8,4 antes vs. 9,9 depois; P < 0,05), enquanto que apenas os participantes do grupo FA apresentaram aumento no peso bruto fecal (71,5 g vs. 126 g; P = 0,020) e no percentual de água nas fezes (74,5% vs. 78,4%; P = 0,038). A qualidade de vida mensurada pelo WHOQOL-Bref não diferiu em nenhuma intervenção. O tratamento com FA aumentou significativamente a população de bactérias do gênero Bacteroides e Prevotella, Faecalibacterium prausnitzii e Bifidobacteriums sp, enquanto que ambos FA e F reduziram a contagem das bactérias do gênero Desulfofibrio. Conclusões: Em voluntários sadios, o aumento no consumo de fibras e água melhorou o hábito intestinal, mas foi acompanhado de sintomas abdominais, particularmente quando o aumento na ingestão de fibras não foi acompanhado por aumento no consumo de água. O efeito na microbiota também foi superior no grupo tratado com fibra e água. / Background and aims: Intestinal physiology can be influenced by changes in fiber and water intake. This simple concept supports the recommendation of increasing fiber and water ingestion for treatment of bowel constipation. The aim of our study was to test whether such recommendation is true in healthy volunteers. Methods: In this open label clinical trial, 20 healthy participants had their basal characteristics determined (diet, bowel function, quality of life and intestinal microbiota), followed by randomization for 14 days treatment with increased fiber consumption (group F) or increased fiber and water intake (group FW), with reassessment of the variables at the end. Results: Nineteen participants were analyzed (10 F and 9 FW). The majority of them (68.4%) developed one or more abdominal symptoms during the treatments, particularly the group F as compared to FW (90% vs. 44%; P = 0.034). Both groups showed increased number of evacuations per week (group F: 6.8 before vs. 8.8 after; group FA: 8.4 vs. 9.9; P < 0.05), whereas group FW presented an increase in both fecal weight (71.5 g vs. 126 g; P = 0.020) and water percentage in feces (74.5% vs. 78.4%; P = 0.038). Quality of life measured by WHOQOL-Bref did not differ in any intervention. Participants receiving FW had a significant increase in bacteria from the Bacteroides and Prevotella genus, Faecalibacterium prausnitzii and Bifidobacterium, whereas both FW and F had a reduced number of Desulfofibrio. Conclusions: In healthy volunteers, a higher intake of fiber and water improved the bowel function but was accompanied by abdominal symptoms, particularly when the dietary fiber was introduced without changes in water intake. The effect on fecal microbiota was superior in participants treated with fiber and water.

Objetivo: Avaliar a influência da localização da enterocolite necrosante neonatal na mortalidade de recém-nascidos (RN) submetidos à laparotomia exploradora. Métodos: Estudo de coorte prospectiva de 141 recém-nascidos com ECN submetidos consecutivamente à laparotomia exploradora no período de novembro de 1991 a dezembro de 2005. Foram avaliados dados epidemiológicos, localização e extensão da doença, crescimento intra-uterino e o número de óbitos no período de 60 dias após a cirurgia. Resultados: Setenta e quatro (52,5%) crianças eram do sexo masculino, com peso médio de nascimento de 1.589 ± 665 gramas, com idade gestacional média de 33,6 ± 2,9 semanas. Prematuridade ocorreu em 84,4% (119/141) dos RN. Cinqüenta e sete (40,4%) eram pequenos para a idade gestacional. Óbito ocorreu em 68 crianças (48,2%). Na análise bivariada, observou-se que o comprometimento do jejuno-íleo foi associado com alta mortalidade (20 óbitos - 76,9%; OR = 20; intervalo de confiança de 95% = 4,6 - 96,3; p < 0,001) e que a doença no jejuno estava associada à maior extensão da ECN. Entretanto, no modelo de regressão logística múltipla com controle individual de cada variável, a doença no jejuno-íleo (OR = 0,61; intervalo de confiança de 95% = 0,06 - 6,14; p = 0,68) e no intestino grosso (OR = 2,91; intervalo de confiança de 95% = 0,81 - 10,50; p = 0,10) não foram consideradas fatores de risco para o óbito. Conclusões: Em análise adequada, com controle isolado de cada variável estudada, a mortalidade foi independente da localização da ECN no intestino delgado ou no intestino grosso. Porém, a localização da doença no jejuno foi um marcador de maior extensão da ECN e, conseqüentemente, de pior prognóstico. Extensão difusa da doença e recém-nascidos PIG foram os mais importantes fatores de risco de ocorrência de óbito nesses recém-nascidos submetidos à cirurgia. / Aim of the study: To evaluate the effect of disease site on the mortality rate of newborns with necrotizing enterocolitis (NEC) undergoing exploratory laparotomy. Methods: Prospective cohort of 141 consecutive newborns with NEC who underwent laparotomy from November 1991 to December 2005. The study variables included epidemiologic data, disease site and extent, intrauterine growth, and number of deaths in the 60 days after operation. The protocol was approved by the institution’s Research Ethics Committee. Main results: Seventy-four (52.5%) infants were male. Mean birth weight was 1,589 ± 665 g, and mean gestational age was 33.6 ± 2.9 weeks. One-hundred and nineteen (84.4%) newborns were premature. Small for gestational age was observed in 57 (40.4%). Sixty-eight (48.2%) infants died. Bivariate analysis revealed that involvement of the jejunum and ileum was associated with high mortality rates (20 deaths, 76.9%; OR = 20; 95% 95% CI = 4.6 – 96.3; p < 0.001), and that involvement of the jejunum was associated with greater disease extent. After controlling for individual variables, logistic regression showed that the mortality associated with jejunum and ileum involvement (OR = 0.61; 95% CI = 0.06 - 6.14; p = 0.68) did not differ from that associated with large bowel involvement (OR = 2.91; 95% CI = 0.81 – 10.50; p = 0.10); however, jejunum involvement remained significantly associated with disease extent. Conclusions: NEC-related mortality in newborns undergoing laparotomy was not influenced by disease site (small or large bowel). However, jejunum involvement was a marker of greater disease extent and therefore of poor prognosis. Diffuse disease extent and small for gestational age were the most important markers of risk of death in NEC newborns submitted to surgery.

Glicocorticoides e outras drogas imunossupressoras são comumente utilizados para o tratamento de condições inflamatórias, como as Doenças Inflamatórias Intestinais (DIIs). Apesar dos avanços na terapia medicamentosa, a remissão da doença ainda é difícil de ser mantida. Devido às suas propriedades imunomodulatórias, as Células-Tronco Mesenquimais (MSCs – Mesenchymal Stem Cells) têm emergido como reguladoras da resposta imune, e sua viabilidade e propriedades migratórias são essenciais para o sucesso da terapia celular. Entretanto, pouco se conhece sobre os efeitos das drogas convencionalmente utilizadas no tratamento das DIIs no comportamento das MSCs. Portanto, o objetivo deste estudo foi avaliar a viabilidade, a morfometria nuclear, a polaridade celular, a distribuição da actina-F e da FAK (Focal Adhesion Kinase), e o comportamento migratório das MSCs na presença das drogas Azatioprina (AZA) e Dexametasona (DEXA). As células foram isoladas de membranas coriônicas humanas e caracterizadas pela diferenciação em adipócitos e osteócitos, bem como pela expressão de um painel de marcadores de superfície. As MSCs foram previamente tratadas com AZA ou DEXA por 24h ou 7d nas concentrações de 1μM ou 10μM, respectivamente. Ambas as drogas não afetaram a viabilidade celular analisada por MTT (3-(4,5-dimethyltiazol-2-yl)-2,5- diphenyltetrazolium bromide) e morfometria nuclear. Entretanto, a análise do índice de polaridade resultou em uma morfologia mais alongada após o tratamento com AZA, enquanto células mais arredondadas foram observadas na presença de DEXA. Os filamentos de actina foram marcados por Rodamina-Faloidina e sua análise mostrou que a AZA preservou parcialmente a formação de lamelipódios e aumentou a presença de fibras de estresse ventrais, enquanto que a DEXA inibiu a formação de lamelipódios, evidenciou uma maior presença de fibras de estresse ventrais e diminuiu a estabilidade das protrusões de membrana, observadas em vídeo. Através da análise de microscopia de série temporal, foi observado que as células sob o efeito da AZA por 7d migraram por maiores distâncias e tiveram um aumento em sua velocidade de migração (24,35%; P < 0,05; n = 4), ao passo que a DEXA diminuiu a velocidade migratória em 24h e 7d (-28,69% e -25,37%, respectivamente; P < 0.05; n = 4) e diminuiu a distância alcançada pelas células. Em conclusão, nossos dados sugerem que as drogas AZA e DEXA podem afetar diferentemente a morfologia e o comportamento migratório das MSCs, possivelmente afetando o resultado da terapia celular. O protocolo de migração celular utilizado neste estudo foi estabelecido por nosso grupo de pesquisa, sendo que um artigo científico contendo todas as etapas do protocolo foi escrito para que outros laboratórios possam utilizá-lo de maneira simples e eficaz. / Glucocorticoids and other immunosuppressive drugs are commonly used to treat inflammatory disorders, such as Inflammatory Bowel Disease (IBD) and, despite few improvements, the remission of IBD is still difficult to maintain. Due to its immunomodulatory properties, Mesenchymal Stem Cells (MSCs) have emerged as regulators of immune response, and its viability and activation of migratory properties are essential for a successful cell therapy. However, little is known about the effects of immunosuppressant drugs used on IBD treatment on MSCs behavior. In this way, the aim of this study was to evaluate MSCs viability, nuclear morphometry, cell polarity, F-actin and FAK (Focal Adhesion Kinase) distribution and cell migration properties in the presence of the immunosuppressive drugs Azathioprine (AZA) or Dexamethasone (DEX). MSCs were isolated from human chorionic membranes and characterized through adipogenic and osteogenic differentiations, as well as a panel of surface markers. Cells were previously treated with AZA or DEX for 24 hrs or 7 days at 1μM and 10μM, respectively. Both drugs had no effects on cell viability analyzed through MTT (3-(4,5- dimethyltiazol-2-yl)-2,5-diphenyltetrazolium bromide) and nuclear morphometry. However, polarity index analysis showed that AZA treatment induced a more elongated cell shape while a greater presence of rounded cells was observed under DEX exposure. F-actin was stained by Rhodamine-Phalloidin and showed that AZA could partially preserve lamellipodia formation and increase the presence of ventral actin stress fibers, while DEX inhibited lamellipodia formation and increased the presence of ventral actin stress fibers while decreasing protrusion stability, observed in video. Through time-lapse microscopy, it was observed that after 7 days of treatment, AZA improved cell the spatial trajectory (ST) and increased migration speed (24.35%, P < 0.05, n = 4) while DEX impaired ST and migration speed after 24 hrs and 7 days treatment (- 28.69% and -25.37%, respectively; P < 0.05, n = 4). In conclusion our data suggests these immunosuppressive drugs can differently affect MSCs morphology and migration capacity, possibly impacting the success of cell therapy. The migration protocol used in this study was successfully established by our group, leading to the writing of a protocol paper to facilitate the usage of this technique by other laboratories in a simple and efficient manner.

Changes to the composition and function of the gut mononuclear phagocyte (MNP) compartment are associated with the development of intestinal inflammation. Much work has focused on the role of MNPs in gut-associated lymphoid tissue in maintaining homeostasis, however little is known regarding the roles of MNPs during colitis. We have investigated MNPs in the large intestinal lamina propria during the steady state and inflammation. One of our primary aims was to determine the contribution of MNP subsets to intestinal pathology. For our studies of inflammation, we focused mainly on the Helicobacter hepaticus infection &plus; anti-IL-10R model, which induces inflammation of the colon and caecum (typhlocolitis). We defined the composition of the MNP compartment alongside intestinal pathology scores throughout Hh &plus; anti-IL-10R typhlocolitis. Peak pathology, 2-3 weeks after induction of colitis, coincided with peak frequencies of CX₃CR1^int Ly6C^&plus; MNPs. Having observed the accumulation of CX₃CR1^int CD64^&plus; monocyte/macrophage MNPs in the inflamed lamina propria, we conducted comparative whole genome microarray analysis of these cells isolated from the large intestine three weeks after Hh &plus; anti-IL-10R treatment. CX₃CR1^int CD64^&plus; MNPs selectively expressed a variety of pro- and anti-inflammatory genes, including a number of genes which individually can both promote and negatively regulate inflammation. IL-23 is essential for Hh &plus; anti-IL-10R-induced intestinal pathology. We investigated the role of MNPs as a source of IL-23 which drives Hh &plus; anti-IL-10R colitis. Unexpectedly, our results indicate that normally hyporesponsive CX₃CR1^hi macrophages may act as the initial source of IL-23, which induces development of colitis. Recruitment of Ly6C^&plus; MHCII^&plus; MNPs to the lamina propria was IL-23-dependent, and these cells also expressed IL-23, which may establish a positive feedback loop of immune cell recruitment, activation and IL-23 production. Finally, we also examined how MNPs might be recruited to the colonic lamina propria during inflammation. Our studies support the conclusion that CCR6 is not required for accumulation of monocyte-derived populations in the inflamed intestine. We cannot rule out a role for CCR2, however preliminary data from the Hh &plus; anti-IL-10R colitis model suggest a potential role for CCR1 or its close relation CCRL2. Such pathways could represent new therapeutic targets in inflammatory bowel disease.