RESUMO
BACKGROUND: Irritable bowel disease (IBS) is viewed upon as a functional disorder of subclinical inflammatory changes in recent years, and there is no reliable biomarker. Triggering receptor expressed on myeloid cells 1 (TREM-1), also produced in a soluble form (sTREM-1), is involved in the activation of inflammatory cascades of intracellular events and may play a role in pathogenesis of IBS. AIM: To investigate whether serum sTREM-1 level can be used as a marker of subclinical inflammation in D-IBS. METHODS: Abdominal pain was quantified by a validated questionnaire. Expression level of TREM-1 in colonic mucosa as well as sTREM-1 level in serum was also detected. Furthermore, we investigated the involvement of TREM-1-associated macrophage activation in IBS-like visceral hypersensitivity. RESULTS: No evidence for obvious inflammation was found in D-IBS patients. Serum sTREM-1 level in D-IBS patients was significantly higher than that in HCs, which was also significantly correlated with abdominal pain scores. We showed a marked increase in the proportion of TREM-1-expressing macrophages in D-IBS, which was significantly correlated with abdominal pain scores. Functionally, gadolinium chloride (GdCl3), a macrophage selective inhibitor, or LP17, the TREM-1-specific peptide, significantly suppressed the visceral hypersensitivity in trinitrobenzene sulfonic acid (TNBS)-treated mice with IBS-like visceral hypersensitivity. CONCLUSIONS: Serum sTREM-1 level is significantly higher in D-IBS patients and positively correlates with abdominal pain, which may be initiated by TREM-1-associated macrophage activation, indicating the existence of subclinical inflammation in D-IBS. Therefore, serum sTREM-1 is a potential marker of subclinical inflammation in D-IBS.
Assuntos
Diarreia/etiologia , Síndrome do Intestino Irritável/diagnóstico , Receptor Gatilho 1 Expresso em Células Mieloides/sangue , Dor Abdominal/etiologia , Adulto , Animais , Biomarcadores/metabolismo , Western Blotting , Estudos de Casos e Controles , Colo/imunologia , Colo/metabolismo , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Imunofluorescência , Humanos , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/imunologia , Síndrome do Intestino Irritável/metabolismo , Ativação de Macrófagos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Receptor Gatilho 1 Expresso em Células Mieloides/metabolismoRESUMO
Irritable bowel syndrome (IBS) is one of the most prevalent functional disorders in Chile impacting on socio-economic development due to significantly impaired quality of life of the individual. It is characterised by abdominal discomfort associated with alterations in bowel habit and increased visceral hypersensitivity. One of the outstanding features of IBS is the presence of a bi-directional imbalance of gut-brain interactions, which can induce alterations in the intestinal immune response. IBS is characterised by increased intestinal mast cell activity associated with alterations of para-cellular permeability and activation of sensory nerve endings. The increased proximity of mast cell to colonic nerves is correlated with abdominal pain and increased visceral hypersensitivity of the patients. In spite of the well-described role of mast cell in the induction of mucosal inflammation, in IBS only a low-grade inflammation is observed. The present review discuses the possible immune-regulatory mechanisms that are involved in IBS pathophysiology.
El síndrome de intestino irritable (SII) es considerado uno de los trastornos funcionales más prevalente en Chile, que impacta el desarrollo socio-económico del país debido al deterioro de la calidad de vida de los individuos que lo portan. Es caracterizado por molestias abdominales asociadas a alteraciones en el hábito de defecación e hipersensibilidad visceral. Una de las características más destacadas en el SII es la presencia de un desequilibrio de las interacciones en el eje intestino-cerebro, el cual puede inducir alteraciones en la respuesta inmune intestinal. El SII es caracterizado por una aumentada actividad de los mastocitos en el intestino, asociada con alteraciones en la permeabilidad para-celular epitelial y la activación de terminaciones nerviosas en la mucosa intestinal. El aumento de la cercanía de los mastocitos a nervios colónicos está relacionado con el dolor abdominal y la hipersensibilidad visceral de los pacientes. Pese a que está muy bien descrito el papel del mastocito en la inducción de la inflamación en mucosas, en el SII se observa sólo un bajo-grado de inflamación. En la presente revisión se discute los posibles mecanismos regulatorios inmunes que están involucrados en la fisiopatología del SII.
Assuntos
Humanos , Síndrome do Intestino Irritável/fisiopatologia , Síndrome do Intestino Irritável/imunologia , Colo/inervação , Hipersensibilidade , Inflamação , Mastócitos/patologia , Sistema Nervoso/fisiopatologiaAssuntos
Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/imunologia , Imunoglobulina G/sangue , Medicina Baseada em Evidências , Hipersensibilidade Alimentar/dietoterapia , Hipersensibilidade Alimentar/economia , Alemanha , Fidelidade a Diretrizes , Humanos , Síndrome do Intestino Irritável/imunologia , Transtornos de Enxaqueca/imunologia , Valor Preditivo dos Testes , Valores de ReferênciaRESUMO
Life stress and mucosal inflammation may influence symptom onset and severity in certain gastrointestinal disorders, particularly irritable bowel syndrome (IBS), in connection with dysregulated intestinal barrier. However, the mechanism responsible remains unknown. Crowding is a validated animal model reproducing naturalistic psychosocial stress, whose consequences on gut physiology remain unexplored. Our aims were to prove that crowding stress induces mucosal inflammation and intestinal dysfunction, to characterize dynamics in time, and to evaluate the implication of stress-induced mast cell activation on intestinal dysfunction. Wistar-Kyoto rats were submitted to 15 days of crowding stress (8 rats/cage) or sham-crowding (2 rats/cage). We measured spontaneous and corticotropin-releasing factor-mediated release of plasma corticosterone. Stress-induced intestinal chrono-pathobiology was determined by measuring intestinal inflammation, epithelial damage, mast cell activation and infiltration, and intestinal barrier function. Corticosterone release was higher in crowded rats throughout day 15. Stress-induced mild inflammation, manifested earlier in the ileum and the colon than in the jejunum. While mast cell counts remained mostly unchanged, piecemeal degranulation increased along time, as the mucosal content and luminal release of rat mast cell protease-II. Stress-induced mitochondrial injury and increased jejunal permeability, both events strongly correlated with mast cell activation at day 15. Taken together, we have provided evidences that long-term exposure to psychosocial stress promotes mucosal inflammation and mast cell-mediated barrier dysfunction in the rat bowel. The notable resemblance of these findings with those in some IBS patients, support the potential interest and translational validity of this experimental model for the research of stress-sensitive intestinal disorders, particularly IBS.
Assuntos
Aglomeração/psicologia , Trato Gastrointestinal/imunologia , Mucosa Intestinal/imunologia , Mastócitos/imunologia , Meio Social , Estresse Psicológico/imunologia , Animais , Contagem de Células , Colo/imunologia , Corticosterona/sangue , Hormônio Liberador da Corticotropina , Modelos Animais de Doenças , Citometria de Fluxo , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/patologia , Abrigo para Animais , Íleo/imunologia , Imuno-Histoquímica , Mucosa Intestinal/metabolismo , Síndrome do Intestino Irritável/imunologia , Síndrome do Intestino Irritável/psicologia , Jejuno/imunologia , Masculino , Mitocôndrias/metabolismo , Permeabilidade , Ratos , Ratos Endogâmicos WKY , Estresse Psicológico/etiologia , Fatores de TempoRESUMO
Inflammation and mucosal immune system activation have an important role in irritable bowel syndrome (IBS), whereas genetic factors can control some immunological mediators. In this study, a number of polymorphic genes coding for T-helper 1, T-helper 2, and T-regulatory cytokines were genotyped in 71 patients with IBS, and the results were compared with controls. IL-4 CC genotype at position -590, IL-4 TT genotype at position -33, and IL-10 GA genotype at position -1082 were significantly overrepresented in the patients with IBS in comparison with controls (P < 0.001). The frequencies of the following haplotypes in the patient group were significantly higher than in the control group: IL-2 (-330, +160) GT haplotype (P = 0.002), IL-4 (-1098, -590, -33) TCC haplotype (P < 0.001), and TCT haplotype (P < 0.001). While production of cytokines could be affected by genetic polymorphisms within coding and promoter regions of cytokine genes, IL-4 and IL-10 gene polymorphisms could affect individual susceptibility to IBS.
Assuntos
Citocinas/genética , Polimorfismo Genético , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th2/imunologia , Adulto , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Citocinas/metabolismo , Feminino , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Humanos , Interleucina-10/genética , Interleucina-2/genética , Interleucina-4/genética , Irã (Geográfico) , Síndrome do Intestino Irritável/genética , Síndrome do Intestino Irritável/imunologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Medição de Risco , Fatores de RiscoRESUMO
Irritable bowel syndrome remains a bothersome and frustrating disorder that imposes a heavy and growing socio-economic toll on its sufferers, two-thirds of whom are women, and on health care systems. The biomedical community must take a giant step forward into the discipline of women's gastrointestinal health. Efforts and accomplishments, such as the one reported in this month's issue by Cremon et al., are certainly welcome.