Overview of cytokines and nitric oxide involvement in immuno-pathogenesis of inflammatory bowel diseases

Echinococcoses require the involvement of specialists from nearly all disciplines; standardization of the terminology used in the field is thus crucial. To harmonize echinococcosis terminology on sound scientific and linguistic grounds, the World Association of Echinococcosis launched a Formal Consensus process. Under the coordination of a Steering and Writing Group (SWG), a Consultation and Rating Group (CRG) had the main missions of (1) providing input on the list of terms drafted by the SWG, taking into account the available literature and the participants’ experience; and (2) providing independent rating on all debated terms submitted to vote. The mission of the Reading and Review Group (RRG) was to give an opinion about the recommendation paper in terms of readability, acceptability and applicability. The main achievements of this process were: (1) an update of the current nomenclature of Echinococcus spp.; (2) an agreement on three names of diseases due to Echinococcus spp.: Cystic Echinococcosis (CE), Alveolar Echinococcosis (AE) and Neotropical Echinococcosis (NE), and the exclusion of all other names; (3) an agreement on the restricted use of the adjective “hydatid” to refer to the cyst and fluid due to E. granulosus sensu lato; and (4) an agreement on a standardized description of the surgical operations for CE, according to the “Approach, cyst Opening, Resection, and Completeness” (AORC) framework. In addition, 95 “approved” and 60 “rejected” terms were listed. The recommendations provided in this paper will be applicable to scientific publications in English and communication with professionals. They will be used for translation into other languages spoken in endemic countries.

It is widely accepted that inflammatory Bowel disease (IBD) arises from a dysregulated mucosal immune response to the enteric microbiota in the gut of a genetically susceptible individual. No definitive therapies are available for this inflammatory disorder. Therefore it became imperative to develop new strategies for treating this disease. Probiotics have emerged as a potential new therapeutic strategy for IBD, however their exact mechanisms of action is still poorly defined. In this study, we address the potential effect of a probiotic cocktail (Ultrabiotique®) composed of four live bacterial strains (L. acidophilus, L. plantarum, B. lactis and B. breve) to promote recovery from acute colitis. Probiotic was given to mice by oral gavage after the onset of colitis and the establishment of dextran sulfate sodium (DSS)-induced intestinal injury. Clinical parameters were monitored daily, histological scores of colitis and the production of nitric oxide (NO) and interferon-γ (IFN-γ) were determined. In addition, TLR4, NF-κB and iNOS colonic expression were examined. Probiotic treatment ameliorated clinical symptoms and histological scores. NO and IFN-γ production in plasma were decreased by probiotic. These results were associated with reduced TLR4, iNOS and NF-κB expression in colonic tissue. In conclusion, probiotic exerted anti-inflammatory effects and contributed to a rapid recovery of DSS-induced acute colitis.

Colitis associated cancer (CAC) is the colorectal cancer (CRC) subtype that is associated with bowel disease such as ulcerative colitis (UC). The data on role of NF-κB signaling in development and progression of CAC were derived from preclinical studies, whereas data from human are rare. The aim of this work was to study the contribution of NF-κB pathway during UC and CAC, as well as the immunomodulatory effect of all-trans retinoic acid (AtRA). We analyzed the expression of NOS2, TNF-α, TLR4, and NF-κB, in colonic mucosa. We also studied NO/TNF-αmodulation by LPS in colonic mucosa pretreated with AtRA. A marked increase in TLR4, NF-κB, TNF-α, and NOS2 expression was reported in colonic mucosa. The relationship between LPS/TLR4 and TNF-α/NO production, as well as the role of NF-κB signaling, was confirmed by ex vivo experiments and the role of LPS/TLR4 in NOS2/TNF-αinduction through NF-κB pathway was suggested. AtRA downregulates NOS2 and TNF-αexpression. Collectively, our study indicates that AtRA modulates in situ LPS/TLR4/NF-κB signaling pathway targeting NOS2 and TNF-αexpression. Therefore, we suggest that AtRA has a potential value in new strategies to improve the current therapy, as well as in the clinical prevention of CAC development and progression.

The etiology of inflammatory bowel diseases which include ulcerative colitis (UC) and Crohn disease has not yet been clarified. Several hypotheses suggest a change in composition of gut microflora along with an impaired mucosal barrier that lead to excessive mucosal immunologic responses. Increased production of nitric oxide (NO) contributes greatly to the tissue injury caused by chronic inflammation. Evidence indicates that the mucus layer covering the epithelium is altered during UC and experimental colitis. Our aim in this study was to investigate the potential therapeutic effect of probiotic during DSS-induced colitis by modulating the immune system and colonic mucus production. For that purpose, the probiotic formulation Ultrabiotique® (Lactobacillus acidophilus, Bifidobacterium lactis, Lactobacillus plantarum and Bifidobacterium breve) was administered daily for 7 d to mice with colitis. Probiotic supplementation improved clinical symptoms and histological alterations observed during DSS induced colitis. Ultrabiotique® treatment down regulated the NO production by peritoneal macrophages of DSS-treated mice and enhanced mucus production in both DSS-treated and healthy mice. In conclusion, the modification of microflora by the Ultrabiotique® played a beneficial role in maintaining the integrity of the intestinal mucosal barrier and promoted tissue repair.