Cardiotrophin-1 attenuates experimental colitis in mice.

Cardiotrophin-1 (CT-1) holds potent anti-inflammatory, cytoprotective, and anti-apoptotic effects in the liver, kidneys, and heart. In the present study, the role of endogenous CT-1 and the effect of exogenous CT-1 were evaluated in experimental ulcerative colitis. Colitis was induced in CT-1 knockout and wild-type (WT) mice by administration of dextran sulphate sodium (DSS) in the drinking water during 7 days. CT-1 knockout mice showed higher colon damage and disease severity than WT mice. In addition, CT-1 (200 µg/kg/day, iv) or vehicle (as control) was administered during 3 days to WT, colitic mice, starting on day 4 after initiation of DSS. Disease activity index (DAI), inflammatory markers (tumor necrosis factor α (TNF-α), INFγ, IL-17, IL-10, inducible nitric oxide synthase (iNOS)), colon damage, apoptosis (cleaved caspase 3), nuclear factor κB (NFκB) and STAT-3 activation, and bacterial translocation were measured. Compared with mice treated with DSS, mice also treated with exogenous CT-1 showed lower colon damage, DAI, plasma levels of TNFα, colon expression of TNF-α, INFγ, IL-17, iNOS and cleaved caspase 3, higher NFκB and signal transducer and activator of transcription 3 (STAT3) pathways activation, and absence of bacterial translocation. We conclude that endogenous CT-1 plays a role in the defense and repair response of the colon against ulcerative lesions through an anti-inflammatory and anti-apoptotic effect. Supplementation with exogenous CT-1 ameliorates disease symptoms, which opens a potentially new therapeutic strategy for ulcerative colitis.

Portal Hypertension as a Complication of Cystic Echinococcosis: A 20-Year Cohort Analysis.

Cystic echinococcosis (CE) is a parasitic disease caused by the larval forms of species of the tapeworm Echinococcus. The most common location is the liver. To assess the frequency and clinical characteristics of portal hypertension (PH) and the risk factors for PH development, we performed a retrospective observational study of inpatients diagnosed with hepatic CE and PH from January 1998 to December 2018, at Complejo Asistencial Universitario de Salamanca, Spain. Of 362 patients analyzed with hepatic CE, 15 inpatients (4.1%) had a portal vein diameter ≥ 14 mm, and the mean diameter of the portal vein was 16.9 (standard deviation [SD] ±2.1) mm. Twelve patients were men. The mean age was 59.5 years (SD ± 17.8 years). Four patients had ascites (26.6%), four had collateral circulation (26.6%), 14 had hepatosplenomegaly (93.3%), five had esophageal varices (33.3%), four had hematemesis, and three had jaundice. Other causes of PH included hepatitis B virus (1 patient) and hepatitis C virus (1 patient) infections and alcohol abuse (1 patient). The host variables associated with PH development were male sex (odds ratio, 4.6; 95% confidence interval, 1.1-20.9; P = 0.030) and larger cyst size (10.8 ± 6.3 versus 7.6 ± 4.1; P = 0.004). Hepatic CE is an infrequent cause of PH that usually occurs without indications of liver failure. Larger cyst size and male sex were the main risk factors associated with this complication. Mortality was higher for patients with hepatic CE with PH than for patients with hepatic CE without PH.

Preventive Effect of Cardiotrophin-1 Administration before DSS-Induced Ulcerative Colitis in Mice.

Ulcerative colitis is a relatively frequent, chronic disease that impacts significantly the patient's quality of life. Although many therapeutic options are available, additional approaches are needed because many patients either do not respond to current therapies or show significant side effects. Cardiotrophin-1 (CT-1) is a cytokine with potent cytoprotective, anti-inflammatory, and antiapoptotic properties. The purpose of this study was to assess if the administration of CT-1 could reduce colon damage in mice with experimental colitis was induced with 5% dextran sulfate sodium (DSS) in the drinking water. Half of the mice received an i.v. dose of CT-1 (200 µg/kg) 2 h before and 2 and 4 days after DSS administration. Animals were followed during 7 days after DSS administration. The severity of colitis was measured by standard scores. Colon damage was assessed by histology and immunohistochemistry. Inflammatory mediators were measured by Western blot and PCR. CT-1 administration to DSS-treated mice ameliorated both the clinical course (disease activity index), histological damage, inflammation (colon expression of TNF-α, IL-17, IL-10, INF IFN-γ, and iNOS), and apoptosis. Our results suggest that CT-1 administration before induction of colitis improves the clinical course, tissue damage, and inflammation in DSS-induced colitis in mice.