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INTRODUCTION: To study the expression of defensin-5 (RD-5), soluble phospholipase A2 (sPLA2) and lysozyme in the intestine in a rat model of acute liver failure and its relationship with intestinal bacterial translocation (BT). PATIENTS AND METHODS: Sprague-Dawley (SD) rats were divided into two groups. The experimental group was divided into five subgroups according to the lapsing time after the model was established, which were designated accordingly as 8h, 16h, 24h, 48h, and 72h groups. Acute liver failure (ALF) model was induced by intraperitoneal injection of 10% d-galactosamine. The homogenates of mesenteric lymph nodes (MLNs), liver and spleen from each group were cultured in agar to determine the bacterial outgrowth. The mRNA expression of RD-5, sPLA2, lysozyme and the protein expression of sPLA2, lysozyme were determined. RESULTS: No bacteria grew in the organ cultures from the control group while experimental groups had positive cultures. Expression of the RD-5 and sPLA2 mRNA in the experimental groups gradually increased at early time points and peaked 16h after induction of ALF, then progressively decreased. The mRNA expression of lysozyme in the experimental group peaked at 8h after ALF induction, then progressively decreased. Similar results were obtained with Western blot and immunohistochemical staining. DISCUSSION: The immune barrier function of the ileal mucosa in the rat model of acute liver failure was compromised as demonstrated by the decreased expression of RD-5, sPLA2 and lysozyme in Paneth cells along with increased intestinal bacterial translocation.
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Traslocación Bacteriana , Mucosa Intestinal/metabolismo , Intestinos/microbiología , Fallo Hepático Agudo/metabolismo , Muramidasa/biosíntesis , Fosfolipasas A2/biosíntesis , Animales , Modelos Animales de Enfermedad , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Qualitative and quantitative changes in gut microbiota play a very important role in cirrhosis. Humans harbour around 100 quintillion gut bacteria, thus representing around 10 times more microbial cells than eukaryotic ones. The gastrointestinal tract is the largest surface area in the body and it is subject to constant exposure to these living microorganisms. The existing symbiosis, proven by the lack of proinflammatory response against commensal bacteria, implies the presence of clearly defined communication lines that contribute to the maintenance of homeostasis of the host. Therefore, alterations of gut flora seem to play a role in the pathogenesis and progress of multiple liver and gastrointestinal diseases. This has made its selective modification into an area of high therapeutic interest. Bacterial translocation is defined as the migration of bacteria or bacterial products from the intestines to the mesenteric lymph nodes. It follows that alteration in gut microbiota have shown importance, at least to some extent, in the pathogenesis of several complications arising from terminal liver disease, such as hepatic encephalopathy, portal hypertension and spontaneous bacterial peritonitis. This review sums up, firstly, how liver disease can alter the common composition of gut microbiota, and secondly, how this alteration contributes to the development of complications in cirrhosis.
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Traslocación Bacteriana , Microbioma Gastrointestinal , Cirrosis Hepática/microbiología , Animales , Encefalopatía Hepática/etiología , Encefalopatía Hepática/microbiología , Humanos , Hipertensión Portal/etiología , Hipertensión Portal/microbiología , Cirrosis Hepática/etiología , Cirrosis Hepática Experimental/etiología , Cirrosis Hepática Experimental/microbiología , Ganglios Linfáticos/microbiología , Mesenterio , Peritonitis/etiología , Peritonitis/microbiología , RatasRESUMEN
BACKGROUND AND OBJECTIVE: Inflammatory biomarkers are increased in patients with human immunodeficiency virus (HIV) infection. Antiretroviral treatment (ART) improves some parameters but do not normalize them. The aim of this study is to determine those factors (including microbial translocation) associated with higher inflammation in HIV treated patients. PATIENTS AND METHODS: Transversal observational study. INCLUSION CRITERIA: HIV patients receiving ART with an HIV viral load (VL)<400 copies/mL. Selection of patients: consecutively between November 2011 and January 2012. Main variable: plasma levels of interleukin 6 (IL-6) and tumour necrosis factor α (TNF-α). Main explanatory variable: microbial translocation markers (16S ribosomal DNA and sCD14). Patients with IL-6 or TNF-α levels above percentile 75 (group 1) were compared with the rest of patients (group 2). Odds ratio (OR) were determined. RESULTS: Eighty-one patients were included (73% male, median age 45 years, 48% stage C). Twenty-six percent had chronic hepatitis C. Median CD4 cell was 493/mm(3) and 30% had detectable HIV VL. 16S ribosomal DNA was detected in 21% of patients. Factors associated with the higher levels of inflammatory markers were 16S ribosomal DNA (OR 77, P<.0001), sCD14 levels (P<.0001) and history of cardiovascular disease (OR 15, P<.01). In multivariate analysis, associations remained for 16S ribosomal DNA (OR 62, P<.0001) and previous cardiovascular disease (OR 25, P<.01). CONCLUSIONS: In patients with HIV infection receiving treatment, the higher levels of inflammatory markers are associated with microbial translocation and past cardiovascular events.
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Fármacos Anti-VIH/uso terapéutico , Traslocación Bacteriana , Citocinas/sangre , ADN Bacteriano/sangre , ADN Ribosómico/sangre , Infecciones por VIH/sangre , Inflamación/sangre , Adulto , Anciano , Biomarcadores , Enfermedades Cardiovasculares/epidemiología , Comorbilidad , Estudios Transversales , Diabetes Mellitus/epidemiología , Dislipidemias/epidemiología , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/microbiología , Hepatitis C Crónica/sangre , Hepatitis C Crónica/epidemiología , Humanos , Inflamación/epidemiología , Inflamación/microbiología , Masculino , Persona de Mediana Edad , ARN Bacteriano/genética , ARN Ribosómico 16S/genética , Abuso de Sustancias por Vía Intravenosa/sangre , Abuso de Sustancias por Vía Intravenosa/epidemiología , Adulto JovenRESUMEN
Objetivo. Evaluar el efecto protector contra la lesión por isquemia-reperfusión intestinal del pretratamiento con alopurinol en ratas. Materiales y métodos. Se llevó a cabo un experimento controlado en animales. Un grupo de 10 ratas Wistar de características morfométricas comparables se mantuvo en bioterio bajo condiciones controladas por tres días. A cinco animales se les administró 50 mg/kg diarios de alopurinol por vía oral durante los tres días y, una dosis adicional, antes de inducir isquemia intestinal por ligadura quirúrgica durante 60 minutos seguida de 60 minutos de reperfusión. El otro grupo de cinco ratas no recibió el medicamento. Se hizo el análisis histológico de la mucosa intestinal al final del experimento por medio de la clasificación de Chou y se tomaron hemocultivos de la cavidad cardiaca. Resultados. Se encontraron hemocultivos positivos en 20 % de los animales pretratados con alopurinol, en comparación con el 100 % de las ratas control (p<0,0001). Se evidenció lesión profunda en la mucosa intestinal en todos los casos. La administración previa a la injuria de alopurinol redujo significativamente la lesión por isquemia-reperfusión (p<0,001). Conclusiones. La administración de alopurinol antes de la isquemia intestinal, reduce los cambios morfológicos ocasionados por isquemia-reperfusión. El efecto benéfico se demostró con el pretratamiento por tres días.
Objective: To evaluate the protective effect of pretreatment with allopurinol in an intestinal ischemia-reperfusion injury rat model. Materials and methods: A controlled animal trial was conducted; 10 Wistar rats were kept under controlled conditions for three days. One group (n=5) received allopurinol 50 mg/kg per day for the 3-day period and an additional dose immediately prior to surgical mesenteric artery clamping (60 minutes) and reperfusion (60 minutes). The other group (n=5) did not receive the medication. Hystologic analysis of intestinal mucosa by means of Chou grading system was performed, and blood cultures from the heart were withdrawn. Results: Positive blood cultures were found in 20% of the allopurinol group as compared with 100% in the control group (p<0.0001). Deep mucosal lesion was evidence in all cases. Allopurinol pretreatment reduced significantly the ischemia-reperfusion injury (p<0.001). Conclusions: Allopurinol administration prior to intestinal ischemia ameliorated morphologic changes related to the ischemia-reperfusion process. The beneficial effect of allopurinol was demonstrated with pretreatment for three days.
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Isquemia , Daño por Reperfusión , Alopurinol , Radicales LibresRESUMEN
La infección por el VIH-1 se caracteriza por la eliminación de linfocitos T CD4+, particularmente en la mucosa gastrointestinal, que favorece la traslocación microbiana y la hiperactivación inmunitaria, principal mecanismo patogénico en esta infección. Las células Th17 son una subpoblación proinflamatoria de linfocitos CD4+, que producen IL-17, IL-21 e IL-22, y son importantes en la respuesta antimicrobiana, principalmente en el sistema gastrointestinal, donde promueven la restauración de la mucosa. Aunque su eliminación se ha asociado con progresión de la infección por el VIH-1 y por el virus de la inmunodeficiencia de los simios, y han sido descritas como deletérea en autoinmunidad. Su papel en la patogenia de la infección por el VIH-1 no está claramente establecido. Considerando su capacidad funcional, las células Th17 podrían tener un impacto dual, dependiendo de la fase de la infección en que se encuentre el individuo. Actualmente, hay más información que sugiere que estas células tienen un papel benéfico al promover la recuperación de la mucosa intestinal y disminuir la traslocación microbiana, así como la hiperactivación inmunitaria. Sin embargo, su papel patogénico, particularmente promoviendo la replicación viral mediante la producción de citocinas proinflamatorias, no debe descartarse. En esta revisión, se presentan los datos científicos disponibles del efecto de las células Th17 en la patogenia de la infección por el VIH-1.
HIV-1 infection is characterized by a gradual decrease of the immunological competence and a massive depletion of CD4+ T cells, particularly in gut-associated lymphoid tissue, which leads to microbial translocation, contributing to immune hyperactivation, the main pathogenic mechanism during HIV-1 infection. Th17 cells are a proinflammatory CD4+ T cell subset, which produce IL-17, IL-21 and IL-22 and play a pivotal role in host defense, mainly in the gastrointestinal tissue, where they promote antimicrobial responses and gut mucosa restoration. Although Th17 depletion is a hallmark of the progression of the simian and human immunodeficiency viral infections and they have been involved in the pathogenic process in some autoimmune diseases, the role of these cells during HIV-1 infection is not completely understood. Considering their functional potential, Th17 cells could have a dual role, depending on the stage of HIV infection a patient has reached. Currently, most evidence suggests that Th17 cells have a beneficial role by promoting gut mucosa recovery, preventing microbial translocation and decreasing immune hyperactivation. However, the pathogenic role of these cells, particularly, increasing viral replication through the production of inflammatory cytokines should not be ruled out. In this review, scientific evidence regarding the role of Th17 on the pathogenesis of HIV infection is discussed.