Manifestations Of Inflammatory Disease Research Articles

CD30 Discriminates Heat Shock Protein 60-Induced FOXP3+CD4+ T Cells with a Regulatory Phenotype

In many animal models, the manifestations of inflammatory diseases can be prevented by the adoptive transfer of CD4(+)FOXP3(+) regulatory T cells (Tregs). CD4(+)FOXP3(+) Tregs can be obtained by isolation and expansion of polyclonal naturally occurring Tregs or by Ag-specific activation of CD4(+)CD25(-)FOXP3(-) T cells. Two major obstacles are hampering the translation of this latter protocol into therapeutic application. First, there is a lack of knowledge on relevant autoantigens. Second, the resulting population is contaminated with activated CD4(+) T cells that transiently express Forkhead box P3 but gain no regulatory function. Therefore, these cells may not be safe for clinical application. In this study, we demonstrate that highly suppressive FOXP3(+) Tregs can be induced in vitro by the activation of CD4(+)CD25(-) T cells with the self-Ag human 60-kDa heat shock protein (HSP60). The activation induced suppressive FOXP3(+) Tregs can be distinguished by surface expression of CD30 from nonsuppressive FOXP3(+) effector cells. We confirm that the induced CD30(+)FOXP3(+) Tregs recognize HSP60 epitopes and that the induction of Tregs by HSP60 is enhanced by signaling via TLR4 on APCs. These findings have implications for the generation and isolation of pure populations of Ag-specific Tregs, with the potential to prevent and treat human inflammatory diseases.

Kardiovaskuläre Begleiterkrankungen und Komplikationen bei Darmerkrankungen

Vascular diseases are not encountered very often in gastroenterology, though in cases of ischemic colitis a coronary heart disease is often present. In addition, heart diseases such as coronary heart disease, atrial fibrillation, and congestive heart failure are important risk factors for ischemic colitis and should be treated to avoid further ischemic episodes of the gut. The most common extraintestinal manifestations of Crohn's disease and ulcerative colitis are observed in the eye, on the skin, and in the liver region. Involvement of the cardiovascular system does not seem to be very common, though systematic epidemiological data on the significance of these extraintestinal complications--which certainly influence the prognosis--are lacking. Other patients with Crohn's disease or ulcerative colitis suffer from vasculitis, which reflects a further manifestation of inflammatory diseases affecting the cardiovascular system. Another important complication is activation of coagulationfactors, especially during active flare-up of intestinal disease; this can result in thromboembolic events. Systematic studies or investigations on the epidemiology of cardiovascular complications are still lacking, so that an overview of the published data is given. Metastatic tumors of the heart are rare, but there are case reports of cardiac metastases in patients with carcinomas of the colon. Carcinoid heart syndrome, another cardial complication of malignant disease, can prejudice the prognosis of patients with neuroendocrine tumors of the gastrointestinal tract.

The potential role of antiplatelet agents in modulating inflammatory markers in atherothrombosis.

Atherothrombosis is the process that links atherosclerotic lesion development with unpredictable and life-threatening ischemic vascular events such as angina, myocardial infarction, transient ischemic attack, and stroke. Atherothrombosis is triggered when an unstable atherosclerotic lesion is ruptured, leading to platelet activation and thrombus formation. Inflammatory mediators are responsible for lesion instability leading to rupture, and in recent years atherothrombosis and its underlying condition of atherosclerosis have come to be recognized as manifestations of inflammatory disease. Inflammatory mediators may therefore serve as early markers of atherothrombosis. Measurement of early markers may be used to predict future ischemic events and improve risk stratification in patients following diagnosis of atherothrombotic disease. In addition, detection of such markers may help to optimize the use of current therapies to manage atherothrombosis. Molecules that may serve as early markers of atherothrombotic disease include C-reactive protein, CD40 ligand, myeloperoxidase, pregnancy-associated plasma protein and plasminogen activator inhibitor-1. Early indications are that levels of these markers are influenced by therapies currently in use in the treatment of atherothrombotic conditions, including antiplatelet agents. Ongoing studies will provide further insight into routine assessment of inflammatory markers as a guide to the management of patients with atherothrombosis.

CT imaging of peripheral pulmonary vessel disease

The diseases concerning the small pulmonary vessels are difficult to diagnose. Pathologic findings are rarely limited to the small vessels, and a continuum between the involvement of small and large vessels is frequent. Moreover, small vessels can be affected by various disease entities with overlapping radiologic features and a wide spectrum of clinical manifestations. Nevertheless, these various entities can be easily separated into two different groups by imaging techniques, particularly by computed tomography: obstructive and inflammatory diseases. Radiologic findings of obstructive diseases are relatively constant, dominated by the manifestation of pulmonary hypertension. In contrast, radiologic manifestations of inflammatory diseases are often florid and nonspecific. After a recall of the classification of small vessel diseases and the imaging techniques, we show the computed tomography features of the principal diseases involving the small pulmonary vessels by classifying them in these two principal groups.

CT imaging of peripheral pulmonary vessel disease

The diseases concerning the small pulmonary vessels are difficult to diagnose. Pathologic findings are rarely limited to the small vessels, and a continuum between the involvement of small and large vessels is frequent. Moreover, small vessels can be affected by various disease entities with overlapping radiologic features and a wide spectrum of clinical manifestations. Nevertheless, these various entities can be easily separated into two different groups by imaging techniques, particularly by computed tomography: obstructive and inflammatory diseases. Radiologic findings of obstructive diseases are relatively constant, dominated by the manifestation of pulmonary hypertension. In contrast, radiologic manifestations of inflammatory diseases are often florid and nonspecific. After a recall of the classification of small vessel diseases and the imaging techniques, we show the computed tomography features of the principal diseases involving the small pulmonary vessels by classifying them in these two principal groups.

Divergent induction of apoptosis and IL-8 secretion in HT-29 cells in response to TNF-alpha and ligation of Fas antigen.

Colonic epithelial cell injury is the common manifestation of inflammatory diseases of the bowel. One form of epithelial injury is apoptosis. In our study, we investigated the mechanism leading to apoptosis in HT-29 cells in response to TNF-alpha and ligation of Fas Ag. HT-29 displayed a dual response to TNF-alpha and Fas Ag ligation: in combination with IFN-gamma, HT-29 cells underwent apoptosis, whereas independently, these factors stimulated secretion of IL-8. We used this model of immune-mediated epithelial cell injury to elucidate the signals leading to apoptosis in response to TNF-alpha and Fas Ag ligation compared with the signals leading to induction of IL-8 secretion. The model was further used to distinguish signaling differences between TNF-alpha receptors and the Fas Ag in this cell line. The experiments presented here demonstrate that Fas Ag ligation alone led to production of IL-8 by colonic epithelial cells and represented another function mediated by Fas Ag in addition to apoptosis. This study shows that the pathways leading to cell death and IL-8 production in response to Fas Ag ligation and TNF-alpha were similar with regard to their requirements for new gene expression, protein synthesis, and protein kinase activity. Specifically, new gene expression and protein synthesis were not necessary for TNF-alpha- and Fas Ag-mediated apoptosis, but were necessary for TNF-alpha- and Fas Ag-mediated IL-8 secretion. Tyrosine protein kinase phosphorylation was necessary to signal secretion of IL-8 in response to both agonists but it was not necessary for apoptosis. In spite of the similarities between these two agonists, the kinetics of apoptosis via Fas Ag were significantly more rapid than through the TNF-alpha receptor and serve to distinguish these two signals.

The collar button ulcer. A radiologic-pathologic correlation.

The collar button-shaped ulcer is a distinctive radiographic manifestation of inflammatory disease of the GI tract. Its hallmark is mucosal ulceration with undermining submucosal extension limited by the relatively resistant underlying muscle wall. Such a process is commonly associated with ulcerative colitis where it may be seen diffusely in advanced stages of the acute disease. Occasionally, however, it may be seen in any ulcerating inflammatory disease. In the more aggressive transmural diseases, it is likely to be a localized and transient phenomenon. The same pathophysiological mechanism gives rise to the common appearance of benign ulceration anywhere in the GI tract and, particularly, in the undermined gastric ulcer.