Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nasal provocation (NP) in allergic rhinitis patients can elicit a late phase inflammatory response in which interleukins (IL), leukotrienes (LT), and neutrophils have been implicated. Certain antihistamines have been shown to have anti-inflammatory properties. The objective was to determine whether astemizole at 10 mgs/day has any anti-inflammatory characteristics. We clinically evaluated 20 patients with allergic rhinitis and measured nasal IL-8 and LTB4 during NP with increasing doses of grass and ragweed antigen in a double-blind placebo-controlled fashion after a 4-week course of treatment. Clinical symptom scores for sneezing, pruritus, and rhinorrhea were evaluated. Nasal fluid was examined by ELISA and RIA for IL-8 and LTB4 levels along with neutrophil assessment before NP and at 3, 6, and 8 hours. Symptom scores for nasal sneezing, pruritus, rhinorrhea, and nasal LTB4 levels at 6 and 8 hours and IL-8 at 3, 6, and 8 hours were generally lower in astemizole-treated patients compared to those on placebo. Nasal IL-8 levels corresponded to LTB4 levels at diluent and at 6 hours in the placebo group (P = 0.01). The percentage of neutrophils correlated with LTB4 levels at baseline, coefficient = 0.76, P = 0.02 and at 6 hours, coefficient = 0.62, P = 0.035 in the placebo group. This study is the first to demonstrate an effect of astemizole during NP on IL-8 and LTB4 levels with a significant correlation of neutrophil numbers in untreated patients during the nasal late phase response.
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PMID:Late phase response during nasal challenge: effect of astemizole on leukotriene B4 levels. 893 1

Allergic rhinitis involves an early phase, largely mediated through mast cells, and a late phase which involves cellular infiltration and mediator release. In the early phase, mast cells release mediators as a result of antigen cross-linking adjacent immunoglobulin E molecules bound to mast cell surfaces. This results in an accumulation of histamine which gives rise to the characteristic symptoms of rhinitis--sneezing, itching, rhinorrhoea and congestion. The late phase of the allergic response (hours after challenge) involves infiltration of the nasal epithelium by eosinophils, basophils, monocytes and T-lymphocytes, which release leukotrienes, kinins, histamine and a host of other mediators. The most important part of the late-phase response is probably mediated via the production of cytokines (IL-4, IL-5, IL-6, IL-8, GM-CSF and RANTES) by mast cells, TH2 lymphocytes or epithelial cells. The infiltration of tissues by cells normally present only in the blood is brought about by the production of adhesion molecules, such as VCAM-1 and E-selectin, which cause circulating eosinophils, basophils and T-lymphocytes to adhere to endothelial cells before moving through the endothelium into the tissue (diapedesis). Neuronal reflexes also play a role in the allergic response, both by mediating local responses to mediators and possibly playing a part in the activation of T-lymphocytes. The allergic response has also been shown to be less intense in a hot, humid environment, and more marked in a cold, dry environment, possibly due to changes in osmolality of the nasal surface fluid. Similar factors may play a role in the aetiology of non-allergic rhinitis.
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PMID:Pathophysiology of perennial allergic rhinitis. 921 57

The currently available respiratory topical corticosteroids are all effective at reducing the nasal symptoms of itch, sneezing, rhinorrhoea and obstruction associated with allergic rhinitis. The mechanism of action of corticosteroids is related to their anti-inflammatory activities. They have been documented to prevent fluid exudation and reduce the number of circulating inflammatory cells, including lymphocytes, mast cells, basophils, eosinophils, macrophages, and neutrophils. This occurs through multiple mechanisms, e.g. eosinophil infiltration is suppressed by preventing cytokine production, reducing local mechanisms of tissue infiltration, and decreasing eosinophil survival. Furthermore, corticosteroids also reduce preformed and newly-generated mediators (e.g. histamine, tryptase, prostanoids, leukotrienes), and inhibit production of cytokines and chemokines by inflammatory cells (e.g. IL-1 through IL-6, IL-8, RANTES, TNF-alpha, IFN-gamma and GM-CSF). The currently available corticosteroids differ pharmacologically. Fluticasone propionate appears to have the greatest affinity for the glucocorticoid receptor, and binds more quickly and dissociates more slowly from the receptor compared with other corticosteroids, suggesting a more prolonged duration of action. Its increased specificity for respiratory tissue may lead to greater potency with less potential for systemic adverse effects. Fluticasone propionate has been compared with other corticosteroids in animal models for relative topical and systemic potency, and according to these data, it has the most favourable risk-benefit ratio.
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PMID:The pharmacological basis for the treatment of perennial allergic rhinitis and non-allergic rhinitis with topical corticosteroids. 921 61

In order to further evaluate the role of cytokines in the induction of atopic pruritus, leukocytes from 10 atopic eczema patients or 10 nonallergic controls were stimulated in vitro with mite or birch pollen antigen for 1 and 4 days. Subjects were prick-tested with the supernatants, and whealing and itching were evaluated 20 and 60 min later. The supernatants were also examined for the contents of GM-CSF, IL-2, IL-6 and IL-8 by ELISA and TNFalpha. Two hours prior to testing, the antihistamine cetirizine (20 mg) or a placebo tablet were given to the patients according to a randomized, double-blind study protocol. After pricking with antigen-stimulated leukocyte supernatants, 6 of 10 patients but no controls reacted mostly at 20 min with whealing and/or pruritus. In the cetirizine-treated group, no decrease in these skin reactions was seen compared to placebo. Analysis for cytokines showed increased levels of IL-8 in allergen-stimulated samples, with no correlation to the induction of itching or whealing by these supernatants. IL-6 levels were low and variable, and GM-CSF, IL-2 and TNFalpha levels were always below standard values. These data show that leukocytes selectively release IL-8 in response to in vitro antigen stimulation. They furthermore provide additional support for the concept that as yet to be identified products play a role in atopic pruritus.
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PMID:Role of antigen-induced cytokine release in atopic pruritus. 962 7

Desloratadine is a new, selective, H(1)-receptor antagonist that also has anti-inflammatory activity. In vitro studies have shown that desloratadine inhibits the release or generation of multiple inflammatory mediators, including IL-4, IL-6, IL-8, IL-13, PGD(2), leukotriene C(4), tryptase, histamine, and the TNF-alpha-induced chemokine RANTES. Desloratadine also inhibits the induction of cell adhesion molecules, plateletactivating factor-induced eosinophil chemotaxis, TNF-alpha-induced eosinophil adhesion, and spontaneous and phorbol myristate acetate-induced superoxide generation in vitro. In animals desloratadine had no effect on the central nervous, cardiovascular, renal, or gastrointestinal systems. Desloratadine is rapidly absorbed, has dose-proportional pharmacokinetics, and has a half-life of 27 hours. The absorption of desloratadine is not affected by food, and the metabolism and elimination are not significantly affected by the subject's age, race, or sex. There are no clinically relevant interactions between desloratadine and erythromycin, ketoconazole, or grapefruit juice. Desloratadine is not a significant substrate of the P-glycoprotein transport system. Once daily administration of desloratadine rapidly reduces the nasal and nonnasal symptoms of seasonal allergic rhinitis, including congestion. In patients with seasonal allergic rhinitis and concomitant asthma, desloratadine treatment was also associated with significant reductions in total asthma symptom score and use of inhaled beta(2)-agonists. Use of desloratadine in patients with chronic idiopathic urticaria was associated with significant reductions in pruritus, number of hives, size of the largest hive, and interference with sleep and daily activities. Clinical experience in over 2300 patients has shown that the adverse event profile of desloratadine is similar to that of placebo; desloratadine has no clinically relevant effects on electrocardiographic parameters, does not impair wakefulness or psychomotor performance, and does not exacerbate the psychomotor impairment associated with alcohol use.
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PMID:Desloratadine: A new, nonsedating, oral antihistamine. 1129 78

For effective management of atopic dermatitis (AD), it is important to introduce a therapeutic agent, which although having the fewest side effects, has the greatest anti-inflammatory effect. In the course of screening anti-inflammatory agents, we obtained BSASM, a mixture of several plant extracts. This study was designed to investigate the AD-mitigating effect of BSASM in patients, as well as its anti-inflammatory and immunomodulatory effects in an in vitro experiment. The anti-inflammatory effects of BSASM were evaluated by the level of production of proinflammatory cytokines. Clinical evaluation was also done using eczema area severity index (EASI) score in AD patients. BSASM inhibited LPS-induced activation of NF-kappaB promoter. In addition, LPS-induced an increase of IL-8, and the TNF-alpha production in THP-1 cells was also inhibited. These results suggest that BSASM has an anti-inflammatory activity. A clinical study in patients with AD showed that BSASM induced a reduction of EASI score, degree of pruritus, and TEWL on both the antecubital fossa and abdomen. Besides, BSASM had no irritative or allergic effects. Based on these results, we conclude that BSASM has anti-inflammatory and AD-mitigating effects.
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PMID:Evaluation of the anti-inflammatory and atopic dermatitis-mitigating effects of BSASM, a multicompound preparation. 1558 73

Dermatitis is a group of highly pruritic chronic inflammatory skin diseases which represents a major public-health problem worldwide. The prevalence of dermatitis has increased in recent years affecting up to 20% of the general population. Acute skin lesions are characterized by extensive degrees of intercellular edema of the epidermis (spongiosis) and a marked perivenular inflammatory cell infiltrate in the dermis. Keratinocytes within eczematous lesions exhibit a modified expression of proinflammatory cytokines, chemokines and cell-surface molecules. The pathophysiological puzzle of dermatitis is far from being elucidated completely, but skin infiltration of activated memory/effector T cells are thought to play the pivotal role in the pathogeneses. The aim of this study was the set-up of organotypic models mimicking the symptoms of eczematous dermatitis to provide a tool for therapeutic research in vitro. Therefore activated T cells (ATs) were integrated in organotypic skin and epidermis equivalents (SE, EE). These models enabled the reproduction of several clinical hallmarks of eczematous dermatitis: (1) T cells induce keratinocyte apoptosis, which leads to a reduced expression of the adhesion molecule E-cadherin (E-cad) and disruption of the epidermal barrier. (2) Expression of intercellular adhesion molecule-1 (ICAM-1) allows the attachment of leukocytes to epidermal cells. (3) Upregulation of neurotrophin-4 (NT-4) in the epidermis is thought to mediate pruritus in lesions by supporting nerve outgrowth. (4) Elevated levels of pro-inflammatory cytokines (IL-1alpha and IL-6) and chemokines (IL-8, IP-10, TARC, MCP-1, RANTES and eotaxin) amplify the inflammatory response and lead to an influx of secondary immunocells into the skin. The therapeutics dexamethasone and FK506 markedly reduce cytokines/chemokines production and epidermal damaging in these models. These data underline that activated memory/effector T cells induce eczematous changes in this HaCaT cell based organotypic skin equivalent. Furthermore it can be concluded that these models make it possible to investigate targets of therapeutics in skin.
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PMID:In vitro reproduction of clinical hallmarks of eczematous dermatitis in organotypic skin models. 1595 7

Psoriasis is characterised by the presence of neutrophil overactivation and overproduction of interleukin (IL)-6 and IL-8 from keratinocytes. It is now clear that macrolide antibiotics have anti-inflammatory effects, such as inhibition of IL-6, IL-8 and tumour necrosis factor-alpha, perhaps by suppressing the transcription factor nuclear factor-kappaB or activator protein-1, and reduction of neutrophil activity. It is thus possible that macrolides might be a candidate for adjunctive treatment of psoriasis. In this study, we investigated the effectiveness of treatment with the macrolide antibiotic, erythromycin, for skin lesions and pruritus of patients with psoriasis. In total, 60 patients with psoriasis, especially pruritic psoriasis, were included. This was an open-label study and the analysis was on an intention-to-treat basis. Oral macrolide antibiotics and topical corticosteroids were given to the study group of 36 patients. The control group (24 patients) were treated only with topical corticosteroids. After a 4-week treatment period, scores on the Psoriasis Area and Severity Index (PASI) at baseline and at the end of the treatment, and the effectiveness in reducing itching were compared within and between both groups. Although there was no statistically significant difference between the baseline mean PASI of the two groups (P=0.81), there was a statistically significant difference between the mean PASI of the two groups at the end of the treatment (P=0.023, 95% confidence interval: - 3.45 to - 0.27). The comparison of the mean difference in PASI yielded a statistically significant difference (P=0.03, 95% confidence interval 0.73-3.55). Our study suggests that macrolides could be used as one of the adjunctive therapies for psoriasis vulgaris.
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PMID:Efficacy of erythromycin for psoriasis vulgaris. 1739 53

IL-31 is a novel T(h) type 2 cytokine that can induce pruritus and dermatitis in mice resembling human atopic dermatitis (AD). Eosinophil infiltration in skin lesions is a predominant pathological feature of AD. In the present study, we investigated the effects of IL-31 on the activation of human eosinophils and epidermal keratinocytes. Eosinophils and keratinocytes were cultured either together or separately in the presence or absence of IL-31 stimulation. IL-31 could significantly induce the release of pro-inflammatory cytokines IL-1beta, IL-6 and AD-related chemokines CXCL1, CXCL8, CCL2 and CCL18 from eosinophils, via functional cell surface IL-31 receptor. Such induction was further enhanced upon the co-culture of eosinophils and keratinocytes, in which eosinophils were the main source for releasing pro-inflammatory cytokines and chemokines. The presence of transwell inserts in co-culture system demonstrated that the direct interaction between eosinophils and keratinocytes was required for IL-31-induced cytokine and chemokine release. Cell surface expression of adhesion molecule CD18 on eosinophils and intercellular adhesion molecule-1 on keratinocytes was up-regulated in the co-culture, and levels were further enhanced upon IL-31 stimulation. The interaction between eosinophils and keratinocytes under IL-31 stimulation was differentially mediated through intracellular mitogen-activated protein kinases, nuclear factor-kappaB and phosphatidylinositol 3-kinase-Akt pathways. The above findings suggest a crucial immunopathological role of IL-31 in AD through activation of eosinophils-keratinocytes system.
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PMID:Activation of human eosinophils and epidermal keratinocytes by Th2 cytokine IL-31: implication for the immunopathogenesis of atopic dermatitis. 2041 Feb 59

Recent clinical trials with JAK or mammalian target of rapamycin (mTOR) inhibitors in primary myelofibrosis (PMF) have identified pruritus as one of the most treatment-responsive disease traits. However, little is known about the prevalence of pruritus in PMF or its clinical and laboratory correlates. Among 566 consecutive patients with PMF seen at our institution, the presence or absence of pruritus was documented in 90 (16%) and 146 (26%) patients, respectively. Patients with pruritus were less likely to express MPLW515 (0% vs. 10%; P = 0.02) or leukopenia (8% vs. 24%; P = 0.002). The latter association was more pronounced in the absence of JAK2 or MPL mutations. Pruritus also clustered with marked leukocytosis (23% vs. 11%; P = 0.01) and JAK2V617F (71% vs. 59%; P = 0.08). Pruritus did not correlate with karyotype (P = 0.33), risk category per the Dynamic International Prognostic Scoring System (DIPSS)-plus (P = 0.37), DIPSS-plus-adjusted survival (P = 0.41), or leukemic transformation (P = 0.13). Plasma levels of 20 cytokines, which are known to be abnormally expressed in PMF, including IL-1b, IL-2R, IL-6, IL-8, and VEGF, were measured in 63 informative cases and showed no correlations with history of pruritus. We conclude that pruritus is relatively frequent in PMF and is prognostically irrelevant. The pathogenesis of PMF-associated pruritus is not necessarily linked to proinflammatory cytokines but may instead involve molecules that are either granulocyte-derived or influence granulopoiesis. The apparently differential effect of MPL vs. JAK2 mutations on pruritus requires further investigation.
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PMID:Pruritus in primary myelofibrosis: clinical and laboratory correlates. 2208 34


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