Imene Soufli

Crohn’s disease (CD) is a relapsing–remitting inflammatory bowel disease with a progressive course. The aim of our study was to evaluate the relationship between nitric oxide (NO), pro-inflammatory cytokines, and blood count-based ratios in patients with complicated Crohn’s disease as well as the outcome of corticosteroid or anti-TNF-α therapy. In this context, we evaluated the NLR as the ratio of neutrophils count to lymphocytes count, PLR as the ratio of platelets count to lymphocytes count, and MLR as the ratio of monocytes count to lymphocytes count in patients and controls. Furthermore, we assessed NO production by the Griess method in plasma along with iNOS and NF-κB expression by immunofluorescence method in intestinal tissues of patients and controls. In the same way, we evaluated plasma TNF-α, IL-17A, and IL-10 levels using ELISA. Our results indicate that blood count-based ratios NLR, PLR, and MLR were significantly higher in patients compared to controls. In addition, increased systemic levels of NO, TNF-α, and IL-17A and colonic expression of iNOS and NF-κB were observed in the same patients. Interestingly, the high ratio of NLR and MLR as well as NO production were significantly decreased in treated patients. Collectively, our findings suggest that nitric oxide as well as the blood count-based ratios (NLR, PLR, MLR) could constitute useful biomarkers in complicated Crohn’s disease, predicting the response to treatments.

Cystic echinococcosis (CE) is one of the most important zoonotic diseases with a worldwide distribution. It is caused by the larval stage of the dog tapeworm “Echinococcus granulosussensu lato” and constitutes a major economic and public health problem in several countries. Protoscoleces are one component of this larval stage that can interact with both definitive and intermediate hosts. The aim of the present study was to investigate the potential role of using a radio‐attenuated form of these protoscoleces for immunoprophylaxis against experimental murine echinococcosis. However, mice were immunized twice at 15‐day intervals with gamma (γ) irradiated protoscoleces at doses of 0.4, 0.8, 1.2 and 1.4 kGy then challenged with the intact parasites. Macroscopic and histological analyses with cytokine measurements were performed in order to estimate the number and diameter of cysts, microscopic changes and cytokine profile. An improvement in protection against the challenge dose was observed with increasing dose, giving percentages of 47.7, 49, 55.23 and 70.6%, for the 0.4, 0.8, 1.2 and 1.4 kGy‐groups respectively. These data suggest that immunization with radio‐attenuated protoscoleces may induce satisfactory protective immunity by reducing successfully the formation of cysts, caused by challenge infection.

Inflammatory Bowel Disease (IBD) is a term used to describe a group of complex disorders of the gastrointestinal (GI) tract. IBDs include two main forms: Crohn’s Disease (CD) and Ulcerative Colitis (UC), which share similar clinical symptoms but differ in the anatomical distribution of the inflammatory lesions. The etiology of IBDs is undetermined. Several hypotheses suggest that Crohn’s Disease and Ulcerative Colitis result from an abnormal immune response against endogenous flora and luminal antigens in genetically susceptible individuals. While there is no cure for IBDs, most common treatments (medication and surgery) aim to reduce inflammation and help patients to achieve remission. There is growing evidence and focus on the prophylactic and therapeutic potential of probiotics in IBDs. Probiotics are live microorganisms that regulate the mucosal immune system, the gut microbiota and the production of active metabolites such as Short-Chain Fatty Acids (SCFAs). This review will focus on the role of intestinal dysbiosis in the immunopathogenesis of IBDs and understanding the health-promoting effects of probiotics and their metabolites.

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.

To investigate the effect of pomegranate peel aqueous extract (PGE) on the development of secondary experimental echinococcosis and on the viability of Echinococcus granulosus protoscoleces, and the immunomodulatory properties of PGE. Swiss mice were inoculated intraperitoneally with viable protoscoleces. Then, PGE was orally administered daily during cystic echinococcosis development. Cyst development and hepatic damage were macroscopically and histologically analyzed. The production of nitric oxide and TNF-α was assessed in plasma and the hepatic expression of iNOS, TNF-α, NF-κB and CD68 was examined. Moreover, protoscoleces were cultured and treated with different concentrations of PGE. It was observed that in vitro treatment of protoscoleces caused a significant decrease in viability in a PGE-dose-dependent manner. In vivo, after treatment of cystic echinococcosis infected mice with PGE, a significant decrease in nitric oxide levels (P < 0.0001) and TNF-α levels (P < 0.001) was observed. This decline was strongly related to the inhibition of cyst development (rate of hydatid cyst growth inhibition = 63.08%) and a decrease in CD68 expression in both the pericystic layer of hepatic hydatid cysts and liver tissue (P < 0.0001). A significant diminution of iNOS, TNF-α and NF-κB expression was also observed in liver tissue of treated mice (P < 0.0001). Our results indicate an antihydatic scolicidal effect and immunomodulatory properties of PGE, suggesting its potential therapeutic role against Echinococcus granulosus infection.

Inflammatory bowel disease is an immunologically mediated disease. Notably, it is less common in countries where there is a greater risk of exposure to helminths. In our study, we examined the modulatory effect of the laminated layer extracted from the cyst wall of a helminth parasite, Echinococcus granulosus, on dextran sulfate sodium (DSS)-induced colitis in mice. An acute colitis was induced in BALB/c mice using 2.5% w/v DSS in drinking water. The crude extract of E. granulosus laminated layer was injected intraperitoneally daily, starting 3 days before colitis induction. The Disease Activity Index was monitored daily, colon length and weight were measured and histological scores were evaluated. Nitric oxide (NO) and cytokine levels (interferon γ (IFN-γ), tumor necrosis factor α (TNF-α) and interleukin 10 (IL-10)) were assessed by enzyme-linked immunosorbent assay. In addition, the colonic expression of inducible nitric oxide synthase (iNOS) and nuclear factor-κB (NF-κB) was examined. Statistical analyses were performed by one-way analysis of variance and the survival rate was analyzed by the long rank test. Hydatid laminated layer pretreatment significantly improved the clinical symptoms and histological scores (*** p < 0.01) observed during DSS-induced colitis and maintained mucus production by goblet cells. Furthermore, treatment with hydatid laminated layer caused a significant decrease in NO, IFN-γ (** p < 0.01) and TNF-α production (* p < 0.05) and an increase in IL-10 production. These results were associated with localized downregulation of iNOS and NF-κB expression. Our results demonstrate the potent anti-inflammatory effects of hydatid laminated layer. Furthermore, preventive treatment with the laminated layer played a beneficial role in maintaining the integrity of the intestinal mucosal barrier against DSS-induced injury.