Natural killer cell function and psychological distress in women with and without irritable bowel syndrome

The primary purpose of this exploratory study was to compare percentages of natural killer (NK) cells and activated NK and T cells, and both cytotoxic and in vitro cytokine production activity in women with and without symptomatic irritable bowel syndrome (IBS). A secondary purpose was to examine the relationships of psychological distress and low sense of coherence with immune function indicators and stress hormones. NK cell percentage and activity have been shown to vary in response to many psychological and physiological stressors. The authors compared 2 groups of women: symptomatic IBS (n = 12) and control (n = 12). Between-subject variability for all immune measures was large. The percentage of activated NK and Tcells was significantly lower in the IBS group compared to control (Mann-Whitney U = 30, P = 0.05). Relationships were significant between activated NK and T cell percentage and depression, anxiety, and overall distress (r = -0.54, -0.49, and -0.47, respectively, P < 0.03) and between interferon-gamma production and anxiety (r = -0.45, P < 0.03). There was a trend toward a positive relationship between sense of coherence and NK cytotoxicity (r = 0.39, P = 0.11). Thesefindings are important because they suggest that nursing interventions targeting ongoing physical and psychological distress might also be helpful in improving immune function.     

CCR4-dependent regulatory T cell function in inflammatory bowel disease

Inflammatory bowel disease (IBD) is an idiopathic inflammatory disease of the intestine. CD4(+) T lymphocytes play an important role in both initiating and regulating intestinal inflammatory immune responses. CD4(+)CD25(+)CD45RB(low) regulatory T (T reg) cells are capable of preventing the development of colitis in a mouse model of IBD. The precise mechanism of T reg cell-mediated prevention of colitis in this model is unclear, and the role of chemokine receptors in the trafficking and function of T reg cells in this model has not been determined. We examined the role of the chemokine receptor CCR4 in in vivo trafficking and suppressive function of T reg cells in a mouse adoptive transfer model of IBD. CCR4-deficient T reg cells failed to accumulate in the mesenteric lymph nodes (MLNs) at early time points (2-5 d) after adoptive transfer, resulting in a failure to suppress the generation of pathogenic T cells and the development of colitis. Moreover, although CCR4-deficent T cells had equivalent in vitro suppressive activity and accumulated in MLNs at later time points (42-56 d), they were unable to suppress colitis. Our study demonstrates that CCR4 plays an important role in T reg cell trafficking in LNs and that this is critical for T reg cell suppressive function in vivo.     

Investigating cell therapy for inflammatory bowel disease

ABSTRACT

Introduction: Advances in immuno-modulatory therapies, including anti-TNF-α therapies, have greatly increased the chance to achieve long-term remission of inflammatory bowel disease (IBD) patients. However, as the importance of mucosal healing has been demonstrated in a number of clinical studies, new cell-based therapies that can regenerate and fully restore the intestinal mucosal functions are currently under development.

Area covered: In this review, we feature the recent challenges of cell-based therapies that are applied to the treatment of IBD. In particular, we will focus on hematopoietic stem cells (HSC), mesenchymal stem cells (MSCs) and intestinal stem cells (ISCs) as the candidate source for cell-based therapy targeted to treat IBD. The current status, as well as the expected advantages and disadvantages of those transplantations will be summarized and discussed.

Expert opinion: Transplantation of HSC, MSC and ISC may have different levels of potential in their ability to exert an immunomodulatory or pro-regenerative effect. Combined cell therapies, such as co-transplantation of MSC and ISC, may provide improved therapeutic outcome compared to transplantation of a single cell population. Those cell-based therapies may not only improve the disease activity or tissue regeneration, but may also have the potential to decrease the risk of developing colitis-associated cancers.     

炎症性肠病患者凝血指标变化及其临床意义研究

目的探讨炎症性肠病(IBD)患者凝血指标的变化,及其与疾病活动程度的关系。方法回顾性分析2012年3月至2015年3月就诊的67例IBD患者及50例健康者血小板计数(PLT)、血小板平均体积(MPV)、凝血酶时间(TT)、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)等指标检测结果,比较患者与健康者的差异,不同病情程度患者之间的差异,以及各指标与疾病活动指数的相关性。结果与健康者相比,IBD患者PLT、PT和FIB升高,MPV下降;不同病情严重程度溃疡性结肠炎患者间PLT、MPV、PT和FIB水平比较差异有统计学意义(P0.05),不同病情严重程度克罗恩病患者间PLT、MPV和FIB水平比较差异有统计学意义(P0.05);PLT和FIB与IBD疾病活动指数呈正相关,MPV与疾病活动指数呈负相关。结论 IBD患者体内凝血功能异常,表现为PLT升高、MPV下降,PT延长及FIB升高,PLT、MPV和FIB或可作为判断IBD疾病活动性的指标。     

Natural killer cell frequency and function in patients with monoclonal gammopathies.

We evaluated the frequency and the functional activity of peripheral blood mononuclear cells (PBMCs) with natural killer (NK) cell phenotype in patients with monoclonal gammopathies. CD16+ and CD56+ PBMCs were strongly increased in monoclonal gammopathies of undetermined significance (MGUS) and multiple myeloma (MM). Furthermore, increased frequency of CD16+/CD3+ PBMCs was found in 7/15 patients with MGUS, indicating that T lymphocytes with NK-like phenotype are expanded in at least a subset of these patients. However, despite the increased frequency of PBMCs with natural killer phenotype, the functional NK activity was as comparable in both MGUS and MM patients as in normal individuals. The discrepancy between the expansion of circulating NK cells and the normal NK activity in patients with monoclonal gammopathies requires further investigation. However, at least in some MGUS patients, this discrepancy could be accounted for by the expansion of PBMCs with the rare phenotype CD16/CD3 which have been reported not to mediate significant NK activity.     

Natural killer cell activity and lymphocyte subsets in parenteral heroin abusers and long-term methadone maintenance patients

We studied natural killer (NK) activity and lymphocyte subsets in 11 active parenteral heroin abusers, 11 long-term methadone-maintained former heroin abusers and 11 apparently healthy individuals. All subjects were males aged 23 to 49 and none had active infectious or inflammatory diseases. All current or former heroin abusers were seronegative for antibody to human immunodeficiency virus. The methadone maintenance patients were socially rehabilitated and had not abused drugs parenterally for at least 10 years. NK activity was determined by a standard Cr-release cytotoxicity assay using K562 cells as targets, and lymphocyte subsets were determined by direct immunofluorescence using flow cytometry. At all three effector-target ratios (100:1, 50:1 and 25:1), NK activity was reduced significantly (P less than .01) in parenteral heroin abusers compared with methadone maintenance patients and apparently healthy individuals. The latter two groups did not differ from each other. Parenteral heroin abusers also had higher absolute numbers of CD2, CD3, CD4 and CD8-positive cells. These data support our hypothesis that significant abnormalities of cellular immunity in parenteral heroin abusers can be normalized by successful long-term methadone treatment.     

Colonoscopy in inflammatory bowel disease

This article discusses the important role endoscopy plays in the diagnosis and management of inflammatory bowel disease and how the procedure adds crucial information to the constellation of history, physical examination, radiographic findings, and laboratory values. Differentiation between Crohn's disease and ulcerative colitis has important ramifications for medical therapy, surgical options, and prognosis. This distinction can be accurately made in at least 85% of patients.     

Angiogenesis in inflammatory bowel disease

Both ulcerative colitis and Crohn's disease, the two major forms of inflammatory bowel diseases, are recognized, at the moment, as perplexing and challenging clinical entities, in which several molecules and cell types are implicated. Recent molecular evidence proposes the intestinal microvascular remodelling or angiogenesis, as a phenomenon implicated in the pathogenesis of these chronic inflammatory disorders, together with other proposed theories involved in the pathogenesis of inflammatory bowel diseases, such as genetic, microbacterial and immune factors. Intestinal damage is followed by a physiological angiogenesis, but the abnormal expression of pro- and anti-angiogenic molecules and the changes of vascular cell types could reflect a pathological vascular remodelling. Thus, the inflammation may be favoured and maintained by a pathological angiogenesis. A better understanding of the angiogenic process may facilitate the design of more effective therapies for chronic intestinal inflammation.     

Advances in inflammatory bowel disease

Optimal management of patients with IBD requires a multidisciplinary approach involving primary care physicians, gastroenterologists, surgeons, radiologists, and nutritionists. The rapidly evolving medical armamentarium promises better quality of life for patients afflicted with these complex, chronic diseases. It is expected that future development of biologic agents will add to the therapeutic options, although it may complicate treatment algorithms. Surgical advancements, particularly in ileoanal anastomosis and bowel preservation by strictureplasty, have improved outcome dramatically. The focus on development of new therapies and refinement of older ones demands a constant attention to the latest peer-reviewed literature and that the clinician keep abreast of the various advancements that have been summarized here.     

Immunotherapy in inflammatory bowel disease

Inflammatory bowel disease affects an increasing number of patients worldwide and is associated with significant morbidity. The dysregulation of the immune system with increased expression of proinflammatory cytokines and increased mucosal expression of vascular adhesion molecules play an important role in its pathogenesis. Strategies targeting TNF-alpha and alpha4-integrin have led to the development of novel therapies for treatment of patients with IBD. This article discusses the efficacy of immunologic agents currently approved for treating Crohn disease and ulcerative colitis and reviews the risks and challenges associated with their use.     

Isoflavones and inflammatory bowel disease

Isoflavones constitute a class of plant hormones including genistein, daidzein, glycitein, formononetin, biochanin A, and irilone, and the major source of human intake is soybeans. Inflammatory bowel disease (IBD) is a chronic recurrent inflammatory disease including ulcerative colitis, Crohn’s disease, and indeterminate colitis, which seriously affects the quality of life of patients and has become a global health problem. Although the pathogenesis of IBD is not very clear, many factors are thought to be related to the occurrence and development of IBD such as genes, immunity, and intestinal flora. How to control IBD effectively for a long time is still a problem for gastroenterologists. Diet has an important effect on IBD. Patients with IBD should pay more attention to diet. To date, many studies have reported that isoflavones have both good and bad effects on IBD. Isoflavones have many activities such as regulating the inflammatory signal pathways and affecting intestinal barrier functions and gut flora. They can also act through estrogen receptors, as they have a similar structure to estrogen. Isoflavones are easy to get from diet for human. Whether they are valuable to be applied to the treatment of IBD is worth studying. This review summarizes the relationship between isoflavones and IBD.     

Irritable bowel syndrome and inflammatory bowel disease in pregnancy

Irritable bowel syndrome and inflammatory bowel disease are gastrointestinal disorders affecting young adults. The peak incidence of irritable bowel syndrome and inflammatory bowel disease is in the late adolescence and early adult years, the time during which many women are planning and beginning their families. Since the potential for life-altering changes and pregnancy complications exist with these diseases, affected pregnant women present a challenge for the gastroenterologist, pregnancy provider, and nurses caring for them. This article outlines what is known about these diseases and their effect on fertility and pregnancy as well as their clinical management during pregnancy.     

Natural killer cells in coeliac disease

Lymphoma is a well recognized but unexplained complication of coeliac disease. Natural killer (NK) cells are a distinct population of lymphocytes with the capacity to lyse some tumour cell-lines in vitro and there is evidence that they may play a role in immune surveillance and protection against the development of malignancy. Using a monoclonal antibody (Leu 11b) and a functional assay, we have measured NK cell numbers and activity in 32 patients with treated coeliac disease (9 of whom had evidence of hyposplenism), 10 splenectomized subjects, 14 biopsied, control patients and 26 normal subjects. The proportions (mean +/- SD) of Leu 11b + cells in normals (17 +/- 5%) and coeliac patients (19 +/- 7%) were similar. NK activity in all the coeliac patients (34 +/- 15%) was not significantly different from normal (31 +/- 15%) and control (26 +/- 15%) subjects. NK activity was correlated with % Leu 11b + cells (r = 0.64; p less than 0.01). The NK activity in patients with hyposplenism associated with coeliac disease (32 +/- 18%) and after splenectomy (29 +/- 15%) was similar to that in normals. We conclude that the increased risk of malignancy in patients with coeliac disease is not due to deficient NK cell numbers or activity.     

Antimycobacterial chemotherapy in inflammatory bowel disease

We report on a case, ulcerative colitis and another of Crohn's disease. During a relapse which was unresponsive to conventional therapy, acid-fast bacilli were found in colonic biopsies. Conventional therapy was substituted with antimycobacterial chemotherapy (rifampicin, isoniazid and ethambutol) which was responsible for a marked improvement. However, a relapse occurred during chemotherapy and no acid-fast bacilli were found. The patients became responsive to sulphasalazine and corticosteroid therapy once again. It appears that Mycobacteria play a collateral role in inflammatory bowel disease and that once they have been eliminated the original disease re-emerges.     

Computational models in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic and relapsing disease with multiple underlying influences and notable heterogeneity among its clinical and response‐to‐treatment phenotypes. There is no cure for IBD, and none of the currently available therapies have demonstrated clinical efficacies beyond 40%–60%. Data collected about its omics, pathogenesis, and treatment strategies have grown exponentially with time making IBD a prime candidate for artificial intelligence (AI) mediated discovery support. AI can be leveraged to further understand or identify IBD features to improve clinical outcomes. Various treatment candidates are currently under evaluation in clinical trials, offering further approaches and opportunities for increasing the efficacies of treatments. However, currently, therapeutic plans are largely determined using clinical features due to the lack of specific biomarkers, and it has become necessary to step into precision medicine to predict therapeutic responses to guarantee optimal treatment efficacy. This is accompanied by the application of AI and the development of multiscale hybrid models combining mechanistic approaches and machine learning. These models ultimately lead to the creation of digital twins of given patients delivering on the promise of precision dosing and tailored treatment. Interleukin‐6 (IL‐6) is a prominent cytokine in cell‐to‐cell communication in the inflammatory responses’ regulation. Dysregulated IL‐6‐induced signaling leads to severe immunological or proliferative pathologies, such as IBD and colon cancer. This mini‐review explores multiscale models with the aim of predicting the response to therapy in IBD. Modeling IL‐6 biology and generating digital twins enhance the credibility of their prediction.     

Serologic markers in inflammatory bowel disease

Inflammatory bowel disease (IBD) is an enduring disease involving mostly young people, with symptoms of bloody diarrhea and abdominal cramps. Several antibodies have been associated with IBD, the 2 most comprehensively studied being autoantibodies to neutrophils (atypical perinuclear anti-neutrophil cytoplasmic antibodies) and anti-Saccharomyces cerevisiae antibodies. This review focuses on the value of these antibodies for diagnosing IBD, differentiating Crohn disease from ulcerative colitis, indeterminate colitis, monitoring disease, defining clinical phenotypes, predicting response to therapy, and as subclinical markers. Pancreatic antibodies and newly identified anti-microbial antibodies (anti-outer membrane porin C, anti-I2, and anti-flagellin) are also reviewed.     

Drug-induced nephrotoxicity in inflammatory bowel disease

Conservative management of inflammatory bowel disease (IBD) is based on a combination of drugs, including aminosalicylates (ASAs), steroids, antibiotics, immunosuppressives and biologic agents. Although various side effects have been related to treatment regimens, drug-induced nephrotoxicity is rather uncommon. Furthermore, it is often underestimated since renal function deterioration may be attributed to the underlying disease. The nephrotoxicity of ASAs and cyclosporine A seems well established, but recent data have suggested a possible role of biologic agents such as infliximab and adalimubab in renal impairment. The aim of this review is to summarize the nephrotoxic effects of medical treatment as well as to express possible caveats in the administration of novel agents in IBD.