Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042109 (urticaria)
 6,569 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to investigate the characteristic cytokine pattern of patients with chronic idiopathic urticaria. Using flow cytometry, we examined the frequency of IL4, IL-10, IL-13 and IFN-gamma producing CD4+ and CD8+ T cells in the peripheral blood mononuclear cells at a single cell level. In patients with chronic idiopathic urticaria, the frequency of IL-10 producing CD4+ and CD8 + T cells was significantly higher than that of control subjects, while the frequency of IFN-y producing helper and cytotoxic T cells was significantly lower. The proportion of IL-4 producing CD4 + T cells from patients with urticaria was significantly lower. The ratio of IL-4 producing CD8 + T cells and the proportion of IL-13 producing CD4 + and CD8 + T lymphocytes did not show any significant difference between patients and controls. In our study, we could observe neither a dominant Th1 nor a dominant Th2 type cytokine pattern. We found a significant elevation in the intracellular IL-10 level which may be the cause of the down-regulated Th1 and Tc1 and partly Th2 lymphocyte functions.
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PMID:Cytokine production of CD4+ and CD8+ peripheral T lymphocytes in patients with chronic idiopathic urticaria. 1236 Nov 27

Antiallergic drugs and antihistamines have been widely used for controlling mucosal allergic diseases in which eosinophilia is prominent. Although H1-receptor antagonists are effective for treating histamine-induced wheal and itch in urticaria, the effects of antihistamines and antiallergic agents on other eosinophilic skin diseases remain to be determined. We investigated the effects of oral administration of antiallergic drugs and antihistamines, such as suplatast tosilate, emedastine difumarate, and azelastine hydrochloride, on a novel murine model of eosinophilia in contact sensitivity to picryl chloride. Among the drugs tested, only suplatast tosilate remarkably inhibited blood and tissue eosinophilia and the ear swelling responses. The inhibitory effects on eosinophilia seemed to be mediated by the suppression of IL-5 production in spleen cells during eosinophil development, while the effects on the ear swelling response seemed to be mediated by suppression of IL-4 production in immune lymph node cells in the efferent phase. Suplatast tosilate may effectively treat eosinophilic skin diseases in which Th2-cell-derived cytokines are predominant.
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PMID:Suplatast tosilate inhibits eosinophil production and recruitment into the skin in murine contact sensitivity. 1449 49

In approximately one-third of patients with chronic idiopathic urticaria (CIU), autoantibodies against the high-affinity IgE receptor and/ or against IgE can be detected and a wheal-and-flare response can be provoked by the intradermal injection of autologous serum (ASST). In this study we aimed to further characterize the inflammatory response observed in the subgroup of CIU patients with positive ASST and serum-evoked histamine-release in vitro from basophils in comparison with unaffected skin and healthy donors. An immunohistochemical analysis of infiltrating cells (CD4, MPO, EG1, EG2, tryptase), cytokines (IL-4, IL-5, IFN-gamma), chemokines and chemokine receptors (IL-8, CCR3, CXCR3), and adhesion molecules (ICAM-1, VCAM-1, ELAM-1) was performed on seven selected patients (four males and three females; median age: 45 years; range: 22-57) and five healthy donors. Cytokine evaluation was also performed in five psoriatic patients to obtain an additional control. In spontaneous wheals we observed an increased number of CD4+ T lymphocytes when compared with the controls, and an increased number of neutrophils and eosinophils, whereas mast cells did not show a significant variation. A significant expression for IL-4 and IL-5 could only be observed in lesional skin, while IFN-gamma showed a slight expression in the same site. Chemokine receptors CCR3 and CXCR3 did not show a defined polarized response in either lesional or unaffected skin. An increased expression of all cellular adhesion molecules (CAMs) studied was detected in spontaneous wheals. The lack of a significant difference in the expression of tryptase + mast cells, T lymphocytes, IL-8, CXCR3 and CCR3, a few CAMs between the lesional and unaffected skin of CIU patients suggests a wide immunological activation that involves not only lesional tissues, but possibly extends to the whole of the skin's immune system.
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PMID:Infiltrating cells and related cytokines in lesional skin of patients with chronic idiopathic urticaria and positive autologous serum skin test. 1470 3

An imbalance between the Th1 and Th2 arms of the cellular immune system has been reported in several autoimmune diseases but not in chronic idiopathic urticaria (CIU). Peak, total secretion and secretory pattern of the Th1 cytokines (IFNgamma and IL-2) and Th2 cytokines (IL-4 and IL-10) were determined in resting and stimulated peripheral blood mononuclear cells (PBMC) from nineteen CIU patients, six acute urticaria patients and twelve controls. Stimulated IL-4 secretion was significantly reduced in CIU patients as indicated by their five- and three-fold lower peak levels and total IL-4 secretion, respectively. The IL-4 secretory pattern overtime was also markedly different in patients and controls. The late secretion of IFNgamma at 144 h was also reduced in CIU patients. These aberrations were not detectable in AU patients. Secretion of IL-2 was lower in CIU and AU patients as compared to controls while IL-10 secretion was comparable in the three groups. Our data demonstrate for the first time a predominantly reduced IL-4 secretion in CIU patients. This is associated with reduced secretion of both IL-2 and IFNgamma. These findings indicate a generalized down-regulation of both Th1 and Th2 cytokines' secretion in CIU.
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PMID:Low stimulated IL-4 secretion in PBMC from patients with chronic idiopathic urticaria. 1524 96

The exact pathophysiology of chronic idiopathic urticaria (CIU) is not well understood. The concept of autoreactivity has evolved to explain the disease in up to 50% of cases, while the search for other mechanisms is still needed to explain the disease, at least among the remaining subpopulation of non-autoreactive CIU. Therefore, we thought to investigate some aspects of the IgE-dependent, lymphocyte-mediated late-phase response (LPR) of anaphylaxis. We searched for percentages of FcepsilonRII-bearing (CD23+) B and T lymphocytes and correlated this with total IgE serum levels, IL-4 serum levels and the disease severity scores. Twenty-five patients with non-autoreactive CIU and ten healthy control subjects participated in this study. CD23+ B- and T-cells were assessed by flow cytometry, total IgE serum levels were estimated by enzyme linked fluorescent assay (ELFA), IL-4 serum levels were estimated by Enzyme Amplified Sensitivity Immunoassay (EASIA), while disease severity was determined by a daily self-assessment urticaria activity and itching score. Our results showed that the mean values for percentages of CD23+ B-cells (6.7 +/- 2.3%), total IgE serum levels (139.6 +/- 103.9 microg/dl) and IL-4 serum levels (18.3 +/- 14.7 ng/ml) for patients were statistically significant (p = 0.002, 0.013 and 0.008, respectively), when compared with the corresponding values for controls (4.0 +/- 1.7%, 51.5 +/- 25.1 microg/dl, and 5.1 +/- 4.1 ng/ml, respectively), while the difference between the mean percentage of CD23+ T-cells for patients (2.8 +/- 2%) and that for controls (2.1 +/- 0.6%) was non-significant (p = 0.267). Strong positive correlations were detected between percentages of CD23+ B-cells and severity scores (r = 0.678, p = 0.0001), total IgE serum levels (r = 0.756, p = 0.0001) and IL-4 serum levels (r = 0.709, p = 0.0001), while no correlation was detected between CD23+ B-cells and CD23+ T-cells (r= 0.188, p= 0.368). It is concluded, that CD23+ B-cells, regulated by IL-4, may contribute in the pathogenesis of non-autoreactive CIU, by producing high levels of IgE and possibly lymphokines, while CD23+ T-cells may be involved in early antigen recognition. This may have a future therapeutic ramification in this distinct subset of CIU by targeting low-affinity IgE receptors.
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PMID:Increased circulating FcepsilonRII-bearing B-lymphocytes and serum levels of IL-4 in non-autoreactive chronic idiopathic urticaria. 1571 7

The term chronic autoimmune urticaria (CAIU) is used for chronic urticaria in subjects who present a whealing response to the intradermal injection of autologous serum, suggesting the presence of pathogenic antibody activities. In this study, we examined 28 chronic urticaria subjects with positive autologous serum skin test (ASST), all of whom presented autologous serum-induced lesions at different evolutive stages. Punch biopsies were taken from lesional skin of six subjects at 10', eight subjects at 30', six subjects at 60', and four subjects each at 24 and 48 h. Immunological studies focussed on infiltrating cell immunophenotype and related cytokines, chemokines and chemokine receptors, adhesion molecules. Immunohistochemical staining was performed to measure expression of CD3, CD4, CD8, tryptase, eosinophil cationic protein, myeloperoxidase, basophil granular protein, IL-4, IL-5, IL-8, CCR3 and CXCR3, ICAM-1, VCAM and ELAM. Control staining was done on unaffected skin from the patients and normal skin from four healthy donors. The main infiltrating population was represented by neutrophils, seen focally in both unaffected skin (P = 0.001) and healthy controls (P = 0.003). IFN-gamma and IL-5 were expressed focally in autologous wheals. Significant staining for IL-4 was seen at 30'. CCR3 and CXCR3 were expressed less in autologous wheals than in uninvolved skin (P < 0.0001; P = 0.002). Cellular adhesion molecules (CAMs) reached their highest expression at 30' and 60' in induced lesions, and they showed strong expression also in unaffected skin (ICAM-1: P < 0.0001). Our data show that the immunoinflammatory features of ASST-induced wheals involve a prevalent role of lymphocytes (with a mixed Th1/Th2 response), with strong neutrophil infiltration and activity and involvement of the chemokine pathway. We interpreted the finding of inflammatory cells and mediator up-regulation in uninvolved CIU skin as a sign of prolonged and widespread "urticarial status".
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PMID:Chronic idiopathic urticaria: infiltrating cells and related cytokines in autologous serum-induced wheals. 1572 39

P-Selectin expressed on endothelial cells contributes to acute and chronic inflammation by promoting leukocyte tethering/rolling. Despite increasing evidence of P-selectin expression on human umbilical vein endothelial cells in vitro, the regulatory mechanisms of P-selectin expression on dermal endothelial cells in skin diseases are not fully understood. Here, we demonstrate increased expression of P-selectin in dermal vessels of regional skin in urticaria and atopic dermatitis. The present in vitro analyses with human dermal microvascular endothelial cells (HDMECs) revealed that histamine rapidly induced P-selectin expression. Interleukin (IL)-4 and IL-13 induced prolonged expression of surface P-selectin by HDMECs. A combination of tumor necrosis factor-alpha and IL-4 inhibited P-selectin expression. Pretreatment of HDMECs with tumor necrosis factor-alpha followed by incubation with IL-4 markedly increased P-selectin expression. Notably, incubation with substance P alone induced prolonged P-selectin expression. Activation of STAT6 appears to be a key factor in P-selectin expression induced by substance P and IL-4 because treatment with STAT6 decoy oligodeoxynucleotides significantly inhibited P-selectin expression. The present results indicate that novel, complex mechanisms are involved in endothelial P-selectin expression in the skin. STAT6 in dermal endothelial cells appears to be a potent target for controlling cellular infiltrate in allergic and/or neuroinflammatory skin diseases.
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PMID:STAT-6-mediated control of P-selectin by substance P and interleukin-4 in human dermal endothelial cells. 1687 67

In recent years, the demonstration of circulating functional autoantibodies against the high affinity IgE receptor or against IgE themselves in about one-third of patients with chronic idiopathic urticaria has suggested that an autoimmune mechanism might be involved in the pathogenesis of the disease--the so-called chronic autoimmune urticaria (CAIU). In this study we compare findings from serum-induced and spontaneous wheals with regard to immunohistochemical markers of disease activity and discuss whether autologous serum skin test (ASST) may be regarded as an in vivo experimental model of the physiological stimulus causing urticaria skin condition, or if it does not reproduce the whole of the mechanisms operating in the development of spontaneous wheals. By means of immunohistochemical technique, we analyzed specimens from just-developed spontaneous wheals and from serum-evoked wheals of six CAIU patients, to glean information on cellular infiltrate and related cytokines, chemokines, chemokine receptors and adhesion molecules. According to the results of our study, spontaneous urticaria lesions seem to be sustained by a characteristic inflammation pattern where neutrophils, adhesion molecules, IL-8 and chemokine receptors play a main role in flogosis triggering and, consequently, disease development. On the contrary, ASST-induced wheals seem to imply different activities mainly represented by basophil granulocytes and related molecules, i.e. IL-4. Although it represents an efficacious diagnostic instrument to screen CAIU patients, ASST is not an exhaustive model of the many immunopathogenic pathways operating in the development of urticaria lesions, especially with regard to systemic activation networks.
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PMID:Cellular infiltrate and related cytokines, chemokines, chemokine receptors and adhesion molecules in chronic autoimmune urticaria: comparison between spontaneous and autologous serum skin test induced wheal. 1702 35

Gleichs syndrome is characterized by recurrent localized angioedema, hypereosinophilia, elevated levels of IgM, rapid weight gain, itchy urticaria and fever. Little is known about the pathogenesis of this disease. Increased serum levels for IL5, IL6 and C5a have been reported before and during clinical exacerbations. In order to better understand the role of the T cells in Gleichs syndrome we analyzed the intracellular cytokine expression in CD3+ cells of a patient affected by the disease. As hypereosinophilia was documented, we asked whether IL-4 and IL-5 levels were increased, and the intracytoplasmatic expression of these Th2-cytokines was determined. The percentage of T lymphocytes (CD3-gated cells) of both CD8- and CD8+ phenotype expressing different cytokines showed an unusually high percentage of Th2-related cytokine (IL-4, IL-5 and IL-13) expressing T lymphocytes. The two new variants (myeloproliferative and lymphoproliferative) seem to account for hypereosinophilia in patients with hypereosinophilic syndrome (HES). In the lymphroliferative variant, the presence of a clonal CD3-CD4+ Th2 like lymphocyte secreting IL-4 and IL-5 in peripheral blood, may explain the hypereosinophilia and the hyper-IgE. In our study we show that the patient had a lymphoproliferative variant and her T cell had a Th2 type phenotype. Moreover, we suggest that Th2 lymphocytes may play a role in the pathogenesis of Gleichs syndrome. Further studies are needed to evaluate the possibility that a polyclonal aspecific activation of Th2 type cells can lead to hypereosinophilia, IgE production and the other manifestations typical of Gleichs syndrome.
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PMID:High intracytoplasmatic levels of Il-4 and Il-5 in a patient with Gleichs syndrome: case report. 1716 16

Antihistamines are well established as a mainstay for treating allergic diseases, including seasonal and perennial allergic rhinitis as well as other conditions, such as chronic idiopathic urticaria. The development of new antihistamines is a multistage process that includes in vitro and in vivo assessments of the antihistaminic, anti-inflammatory and antiallergic properties of new therapies. Results of these assessments are critical for predicting and establishing the clinical efficacy of an antihistamine. The focus of this article is to review the investigational methods used to assess the efficacy, safety and tolerability of newer histamine H(1)-receptor antagonists. Desloratadine, a new-generation H(1)-receptor antagonist, was chosen to illustrate the use of this model paradigm. Data obtained from two large observational studies are presented, confirming results obtained from clinical trials that the in vitro inhibition of release of inflammatory mediators such as histamine, prostaglandins, leukotrienes and the reduction of secretion of cytokines such as IL-4 and IL-13 at physiological concentrations is reflected in increased efficacy, particularly upon nasal obstruction. A recent discovery that des- loratadine inhibits nuclear factor-kappaB may be the underlying explanation for much of this extra anti-inflammatory activity.
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PMID:Predicting and establishing the clinical efficacy of a histamine h(1)-receptor antagonist : desloratadine, the model paradigm. 1752 64


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