Late Phase Of Allergic Reaction Research Articles

Is the use of intranasal glucocorticosteroids (inGCSs) in children safe?

It's been 40 years since Niels Mygind publication in British Medical Journal on intranasal application of beclomethasonedipropionate aerosol in Allergic Rhinitis. Since then the new era in treatment of allergic and non-allergic upper airway diseases has begun. This publication presents current concepts on application of intranasal glucocorticosteroids in treatment of upper airway diseases and in particular of allergic rhinitis and rhinosinusitis. The non-questionable advantage of intranasal glucocorticosteroids is their strong anti-inflammatory local action with little impact on general health responsible for few and benign side effects. Main way of action of glucocorticosteroids is connected with binding to the intracellular glucocorticosteroid receptor and its impact on nuclear cytoplasmic transcriptional factors. Glucocorticosteroids suppress gene expression of factors responsible for generating and supporting inflammatory processes, pro-inflammatory cytokines and chemokines production, adhesive molecules expression. It appears that glucocorticosteroids has also other mechanisms of action, non-involving intracellular receptors, leading to inhibiting of early and late phase of allergic reaction. At the moment there are following glucocorticosteroids registered in Poland: beclomethasone, budesonide, fluticasone propionate, fluticasone fuorate, mometasonefuorate. Special attention earns fuorates as their lateral fuorate ester chain makes this molecules highly lipophilic, easily absorbed by nasal mucous membranes epithelium and cell membranes phospholipids. This minimizes their general action and maximizes local action. According to current state of knowledge topical glucocorticosteroids are used in the following upper airway diseases with different inflammatory mechanism: allergic rhinitis, non-allergic rhinitis, particularly NARES, acute rhinosinusitis, chronic rhinosinusitis with and without nasal polyps, adenoid hypertrophy and rhinitis in bronchial asthma.

Nerve growth factor – its role in asthma and allergic reactions

Background: Nerve growth factor (NGF) plays an important role in the growth, differentiation and survival of peripheral and central neurons. Beside neurotrophic activity, NGF exerts several effects on the cells of immune system. Recent studies have demonstrated the importance of NGF in asthma and allergic diseases, such as allergic rhinitis and urticaria. Conclusions: Elevated NGF concentrations have been observed in biological fluids of patients with asthma and allergic diseases. The concentration of NGF further rises after sensitization with allergen. Numerous studies have reported NGF synthesis by almost all inflammatory cells. In addition, most inflammatory cells express TrkA and p75 NGF receptors. Since the activation of mast cells with NGF evokes release of histamine within minutes, this could indicate the potential role of NGF in the early stage of allergic reaction. The late phase of allergic reaction is characterized by infiltration of eosinophils. The activation of eosinophils with NGF evokes release of cytotoxic mediators (major basic protein). Several data also suggest that NGF plays a role in airway inflammation, bronchoconstriction, hyperresponsiveness and remodelling, all observed in patients with asthma. All these results indicate that NGF contributes to responses in allergic inflammation and asthma.

Natürlicher Verlauf von eosinophilem kationischem Protein im Nasensekret von Patienten mit saisonaler allergischer Rhinitis

Eosinophil granulocytes play an important role in inflammation of the nasal mucosa. The eosinophil cationic protein (ECP) is a specific eosinophil granule protein. It is released upon activation of these cells. ECP concentration in nasal secretions has been demonstrated to be a good marker for the activity of eosinophilic nasal mucosal inflammation in patients with symptomatic allergic rhinitis. However, the natural course of ECP concentration in nasal secretions under natural allergen exposure has never been investigated. The aim of our study was to evaluate the course of ECP concentration in nasal secretions under natural allergen exposure. We investigated the natural course of ECP levels in nasal secretions of 179 patients with grass or birch pollen-allergic rhinitis at the beginning, during and after (111 patients) the pollen season. Within the first 2 weeks of the season, we noted a significant increase in the ECP concentration and this concentration continued to increase significantly throughout the rest of the season. In contrast, symptom scores significantly increased within the first 3 days of the season without any further significant increase thereafter. Post-seasonally, ECP concentrations decreased significantly within 4 weeks. In conclusion, our investigation provides information about the natural course of ECP in nasal secretions of patients with seasonal allergic rhinitis suggesting that ECP levels reflect the late phase of allergic reaction and confirming other studies which recommend using ECP levels in nasal secretions for monitoring disease activity or therapy control in patients with seasonal allergic rhinitis.

Mucosal Pathophysiology and Inflammatory Changes in the Late Phase of the Intestinal Allergic Reaction in the Rat

Relatively little information exists concerning the late phase of the allergic reaction in the gastrointestinal tract. Here, we characterized jejunal mucosal pathophysiology and inflammation after oral antigen challenge of sensitized rats, and examined the role of mast cells in events after challenge. Sprague-Dawley rats, mast cell-deficient (Ws/Ws), and +/+ control rats were sensitized to horseradish peroxidase, and challenged intragastrically with antigen 14 days later. Jejunal segments were obtained at 0.5 to 72 hours after challenge for functional assessment in Ussing chambers and for morphological assessment by light and electron microscopy. Intestine from sensitized Sprague-Dawley rats demonstrated enhanced ion secretion and permeability at all times after challenge. Electron microscopy revealed abnormal mitochondria within enterocytes and disruption of the epithelial basement membrane associated with influx into the mucosa of mast cells, eosinophils, neutrophils, and mononuclear cells. Many inflammatory cells appeared activated. In contrast, antigen-challenged Ws/Ws rats demonstrated no functional changes or inflammatory cell infiltrate. We conclude that oral antigen challenge of sensitized rats induces sustained epithelial dysfunction. Mast cells mediate both epithelial pathophysiology and recruitment of additional inflammatory cells that may contribute to persistent pathophysiology and symptoms.

Corticoïdes et allergie

Inflammation is constantly observed in allergic reactions. Corticosteroids are most effective in preventing the late phase of allergic reaction. The action of glucocorticosteroids is mediated through glucocorticoid receptors present in the cellular cytoplasm. When activated, glucocorticoid receptors form a dimer and bind to DNA after migration into the nucleus. Interaction to DNA induces changes in the transcription rate, leading to either gene induction or gene repression. Glucocorticoid receptors are also able to interact with transcriptional factors such as AP-1 (activator protein-1) of NF-kappa B (nuclear factor-kappa B). Through these actions glucocorticosteroids are susceptible to modify functions of cells involved in the allergic inflammatory response. They are in particular able to inhibit most of the pro-inflammatory functions of the eosinophils.

The eosinophil and the eye.

Personal studies in allergic eye diseases reviewed in this paper indicate that: 1. An increased number and an abnormal distribution of eosinophils is present in conjunctival biopsies of patients with vernal keratoconjunctivitis (VKC). 2. Eosinophil and eosinophil products, such as ECP, are also increased in tears of VKC patients and, in hay fever conjunctivitis, accumulate during the late-phase of allergic reaction following specific allergen challenge. 3. Circulating eosinophils of VKC patients show a typical activation phenotypic profile which is associated with increased serum level of eosinophil cationic protein and eosinophil-derived neurotoxin/protein X. A clinical study of the modulatory effect of cetirizine on the early and late phase of the allergic reaction as well as on the eosinophil activation and tissue recruitment following conjunctival allergen challenge is reported as an example of the need to evaluate eosinophil functions when investigating anti-allergic drugs. Drugs modulating various aspects of eosinophil function could play a primary role in the treatment of allergic eye disease.

鼻アレルギーにおける鼻汁中，血清中のｅｏｓｉｎｏｐｈｉｌ ｃａｔｉｏｎｉｃ ｐｒｏｔｅｉｎ（ＥＣＰ）ならびにａｒｙｌｓｕｌｆａｔａｓｅ Ｂに関する研究

Recently four tissue toxic proteins namely major basic protein (MBP), eosinophil peroxidase (EPO), eosinophil-derived neurotoxin (EDN), and eosinophil cationic protein (ECP) were found in eosinophilic leucocytes. Although the characteristics of these proteins concerning tissue damage in the local site of type I allergic reaction have been investigated mainly in lower respiratory tract, the actual clinico-pathological roles of these proteins in nasal allergy are not clarified. Contrary, eosinophils also have histaminase, arylsulfatase, phospholipase D, which are considered to act on a negative feedback mechanism in allergic reaction through inactivation of chemical mediators. Therefore, estimation of ECP and simultaneously arylsulfatase B in nasal secretion and the sera from patients with nasal allergy may clarify the dynamics of clinico-pathological state, especially in the late phase of allergic reaction in each patients. ECP concentrations in the nasal secretions from 22 patients and in the sera from 12 patients with nasal allergy were measured by RIA method. The activities of arylsulfatase B in the nasal secretions and the sera were also estimated in the same specimens as ECP by measuring its hydrolytic activity using p-nitro cathecol sulfate as a substrate. The results obtained were as follows; 1) There was a significant correlation between ECP concentrations in the nasal secretions and the severities of clinical symptoms, especially the degree of nasal obstruction. ECP concentrations also significantly correlated to the score of eosinophilic leucocytes in the nasal smears. 2) The serum ECP concentrations significantly correlated to the number of eosinophilic leucocytes in the peripheral blood, and also showed slight tendency of correlation to the severity of clinical symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Conjunctival provocation test as a model for the study of allergy and inflammation in humans.

The clinical response after allergen challenge and immunologic mechanisms leading to tissue inflammation have been extensively studied in the skin, nose and lung of allergic subjects. The present paper reviews personal studies aimed at evaluating clinical, cellular and humoral events after administration of specific allergen to the eye. Specific conjunctival provocation tests performed in grass-sensitive patients caused persisting inflammatory changes in conjunctival scrapings and tear fluid with a significant accumulation of different inflammatory cells depending on the time of observation (neutrophils, 20 min; eosinophils, 6 h; neutrophils, eosinophils and lymphocytes, 12-24 h after provocation). Increasing the dose of allergen resulted in a dose-dependent increase in the number of inflammatory cells recruited. When high doses of allergen were used, the challenge not only induced late-phase histological changes, but also clinical symptoms 6-10 h after provocation. Several mediators of allergic inflammation, such as histamine, C3a des-Arg, leukotrienes B4 and C4, were also present and could be measured in tears after allergen challenge. Our studies represent the first evidence in humans that a late phase of allergic reaction occurs in the eye. They also suggest that the conjunctival provocation test may represent a model for the study of cells and mediators involved in the pathophysiology of allergic inflammation as well as of its pharmacologic modulation.