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The clinical benefits of short-term therapy with glucocorticoids (GC) in patients with inflammatory bowel disease (IBD) are widely known. However, the effects of this treatment towards the re-establishment of the regulatory network in IBD are not fully explored. We have evaluated the immunological effects of the abbreviated GC therapy in experimental colitis induced by 3% dextran sulphate sodium in C57BL/6 mice. Treatment with GC improved disease outcome, constrained circulating leucocytes and ameliorated intestinal inflammation. The control of the local inflammatory responses involved a reduction in the expression of interferon-γ and interleukin-1β, associated with augmented mRNA levels of peroxisome proliferator-activated receptors (α and γ) in intestine. Furthermore, there was a reduction of CD4 + T cells producing interferon-γ, together with an increased frequency of the putative regulatory population of T cells producing interleukin-10, in spleen. These systemic alterations were accompanied by a decrease in the proliferative potential of splenocytes of mice treated in vivo with GC. Notably, treatment with GC also led to an increase in the frequency of the regulatory markers GITR, CTLA-4, PD-1, CD73 and FoxP3, more prominently in spleen. Taken together, our results pointed to a role of GC in the control of leucocyte responsiveness and re-establishment of a regulatory system, which probably contributed to disease control and the restoration of immune balance. Finally, this is the first time that GC treatment was associated with the modulation of a broad number of regulatory markers in an experimental model of colitis., (© 2016 John Wiley & Sons Ltd.)

Dehydroepiandrosterone (DHEA) is a hormone that plays an important role in the modulation of inflammatory responses. However, the precise mechanisms that link the actions of this androgen with protection or susceptibility to inflammatory bowel diseases (IBD) remain uknown. Here we showed that low dose DHEA inhibited proliferation of spleen cells and IFN-у production. The hormone was not toxic to myeloid lineage cells, although it caused necrosis of spleen cells at the intermediate and highest doses in vitro (50 and 100μM). The treatment of C57BL/6 mice with DHEA during colitis induction by dextran sodium sulfate (DSS) led to a reduction in weight loss and clinical signs of disease. There were decreased peripheral blood monocytes on day 6 of DSS exposure and treatment, besides increase in circulating neutrophils in the tissue repair phase. DHEA also led to reduced lamina propria cellularity and restoration of normal colon length. These results were accompanied by decreased expression of IL-6 and TGF-β mRNA, while IL-13 was augmented in the colon on day 6, which was probably related to attenuation of inflammation. There was retention of CD4(+) cells in the spleen after use of DHEA, along with augmented frequency of CD4(+)IL-4(+) cells, decreased CD4(+)IFN-ɣ(+) in spleen and constrained CD4(+)IL-17(+) population in the mesenteric lymph nodes. Moreover, splenocytes of mice treated with DHEA became hyporesponsive, as observed by reduced proliferation after re-stimulation ex-vivo. In conclusion, DHEA modifyies leukocyte activity and balances the exacerbated immune responses which drive local and systemic damages in IBD., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

The adrenal glands are able to modulate immune responses through neuroimmunoendocrine interactions and cortisol secretion that could suppress exacerbated inflammation such as in inflammatory bowel disease (IBD). Therefore, here we evaluated the role of these glands in experimental colitis induced by 3% dextran sulfate sodium (DSS) in C57BL/6 mice subjected to adrenalectomy, with or without glucocorticoid (GC) replacement. Mice succumbed to colitis without adrenals with a higher clinical score and augmented systemic levels of IL-6 and lower LPS. Furthermore, adrenalectomy negatively modulated systemic regulatory markers. The absence of adrenals resulted in augmented tolerogenic lamina propria dendritic cells but no compensatory local production of corticosterone and decreased mucosal inflammation associated with increased IFN-γ and FasL in the intestine. To clarify the importance of GC in this scenario, GC replacement in adrenalectomized mice restored different markers to the same degree of that observed in DSS group. Finally, this is the first time that adrenal-derived hormones, especially GC, were associated with the differential local modulation of the gut infiltrate, also pointing to a relationship between adrenalectomy and the modulation of systemic regulatory markers. These findings may elucidate some neuroimmunoendocrine mechanisms that dictate colitis outcome.

Crohn's disease (CD) and ulcerative colitis (UC) are intestinal disorders that comprise the inflammatory bowel diseases (IBD). These disorders have a significant effect on the quality of life of affected patients and the increasing number of IBD cases worldwide is a growing concern. Because of the overall burden of IBD and its multifactorial etiology, efforts have been made to improve the medical management of these inflammatory conditions. The classical therapeutic strategies aim to control the exacerbated host immune response with aminosalicylates, antibiotics, corticosteroids, thiopurines, methotrexate and anti-tumor necrosis factor (TNF) biological agents. Although successful in the treatment of several CD or UC conditions, these drugs have limited effectiveness, and variable responses may culminate in unpredictable outcomes. The ideal therapy should reduce inflammation without inducing immunosuppression, and remains a challenge to health care personnel. Recently, a number of additional approaches to IBD therapy, such as new target molecules for biological agents and cellular therapy, have shown promising results. A deeper understanding of IBD pathogenesis and the availability of novel therapies are needed to improve therapeutic success. This review describes the overall key features of therapies currently employed in clinical practice as well as novel and future alternative IBD treatment methods.

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a chronic disorder that affects thousands of people around the world. These diseases are characterized by exacerbated uncontrolled intestinal inflammation that leads to poor quality of life in affected patients. Although the exact cause of IBD still remains unknown, compelling evidence suggests that the interplay among immune deregulation, environmental factors, and genetic polymorphisms contributes to the multifactorial nature of the disease. Therefore, in this review we present classical and novel findings regarding IBD etiopathogenesis. Considering the genetic causes of the diseases, alterations in about 100 genes or allelic variants, most of them in components of the immune system, have been related to IBD susceptibility. Dysbiosis of the intestinal microbiota also plays a role in the initiation or perpetuation of gut inflammation, which develops under altered or impaired immune responses. In this context, unbalanced innate and especially adaptive immunity has been considered one of the major contributing factors to IBD development, with the involvement of the Th1, Th2, and Th17 effector population in addition to impaired regulatory responses in CD or UC. Finally, an understanding of the interplay among pathogenic triggers of IBD will improve knowledge about the immunological mechanisms of gut inflammation, thus providing novel tools for IBD control.

Background and Objectives: The rate of mortality during the surgical separation of conjoined twins in the neonatal period is 50% and can reach up to 75% if it occurs in emergency situations. The planning of the surgical separation procedure is detailed and involves imaging assessment, evaluation of cross-circulation and even other surgical preparation procedures, such as skin expansion., Case Report: Eleven-day-old female omphalopagus conjoined twins underwent emergency surgical separation due to the death of one twin caused by sepsis associated to cardiopathy. The liver was shared by the twins and was separated. The surviving twin died six days later., Conclusions: Surgical separation of conjoined twins in the neonatal period must be avoided due to the patients' organic system immaturity. However, emergency situations such as the one described herein can require the procedure to be carried out., (Copyright 2010 Elsevier Editora Ltda. All rights reserved.)

Objectives: The aim was to test the potential use of an extract of Mikania laevigata (popularly known in Brazil as guaco), made from leaves harvested in different months of the year, on neutrophil migration after an inflammatory stimulus and investigate the underlying molecular mechanisms., Methods: We examined the effect of guaco on vascular permeability and leucocyte function in carrageenan-induced peritonitis in mice., Key Findings: Our results demonstrated that guaco extract administered subcutaneously (3 mg/kg) decreased the vascular permeability and also leucocyte rolling and adhesion to the inflamed tissues by a mechanism dependent on nitric oxide. Specifically, inhibitors of nitric oxide synthase remarkably abrogated the guaco extract-mediated suppression of neutrophil migration to the inflammatory site. In addition, guaco extract-mediated suppression of neutrophil migration appeared to be dependent on the production of the cytokines interleukin-1beta and tumour necrosis factor-alpha. One of the major constituents of the guaco extract, coumarin, was able to inhibit the neutrophil migration towards the inflammatory focus., Conclusions: In conclusion the anti-inflammatory effect induced by guaco extract may be by inhibition of pro-inflammatory cytokine production at the inflammatory site.