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Biomedical subjects

B Wallaert

Publications and source records attributed to B Wallaert.

At least 73 records · Page 4Linked to original sources
PubMed2000

Human dendritic cells in the severe combined immunodeficiency mouse model: their potentiating role in the allergic reaction.

Dendritic cells (DCs) are present in the lungs and airways of healthy and allergic subjects where they are exposed to inhaled antigens. After the uptake of antigens, DCs migrate to lymphoid organs where T cells initiate and control the immune response. The migratory properties of DCs are an essential component of their function but remain unclear in the situation of allergic diseases. To better understand the role of DCs in response to allergens, we first investigated their presence in an original experimental model of allergic asthma: the humanized severe combined immunodeficiency (SCID) mouse reconstituted with peripheral blood mononuclear cells from patients sensitive to Dermatophagoides pteronyssinus (Dpt). Human DCs were detected in lungs of mice developing an inflammatory pulmonary infiltrate and appeared to be mainly located in the alveolar spaces. In a second step, human DCs were generated in vitro from monocytes and injected into naive SCID mice exposed or not exposed to Dpt aerosols. Their migratory behavior was explored, as well as their potential role in modulating the IgE production after exposure to Dpt. After exposure to Dpt, the number of DCs present in airways decreased, while it increased into the spleen and thymus of the mice. The IgE production increased in the presence of DCs as compared with mice not injected with DCs. These results suggest that DCs may play a role in the pulmonary allergic reaction developed in response to Dpt in SCID mice.

Adoptive Transfer↗
PubMed2000

Cytokine profile in minor salivary glands from patients with bronchial asthma.

BACKGROUND: T lymphocytes are important components of the bronchial inflammatory cell infiltrate in asthma. Because lymphocytes activated in the respiratory tract recirculate to remote glandular and mucosal sites, we previously studied the histologic features of minor salivary glands (MSGs) in bronchial asthma and found an airway-like inflammation with T-lymphocyte infiltration, the presence of mast cells that were often degranulated, and basement membrane thickening but no eosinophil infiltration. OBJECTIVE: We sought to investigate the cellular infiltration and cytokine profile in MSGs from untreated asthmatic subjects, steroid-treated asthmatic subjects, and control subjects and to compare these values with those found in bronchial biopsy specimens. METHODS: The cellular infiltration was studied by using immunohistochemistry. Cytokine messenger (m)RNA expression for IL-4, IL-5, and IFN-gamma was determined by using in situ hybridization and cytokine immunoreactivity with immunohistochemistry. RESULTS: A significant increase in CD4 and IL-4 mRNA(+) cells was observed in MSGs from asthmatic patients (both untreated and steroid-treated subjects) when compared with control subjects, which correlated with the clinical severity of asthma (FEV(1) and Aas score). In contrast to the bronchi, no IL-5 mRNA expression was observed in MSGs, and no difference was observed for MSG IFN-gamma mRNA between the groups. At the level of MSG protein expression, the 3 cytokines were seen, with a significant increase in IL-4 protein expression in steroid-treated asthmatic subjects compared with untreated asthmatic subjects and control subjects, but there were no differences between the groups in IL-5 and IFN-gamma protein expression. CONCLUSION: The cytokine mRNA expression pattern observed in the MSGs of asthmatic subjects was different from that found in the bronchi, suggesting a different local immune regulation.

Adult↗
PubMed2000

Long-term follow-up of pulmonary function in patients with nasal polyposis.

The outcome of asthma and/or nonspecific bronchial hyperresponsiveness (BHR) associated with nasal polyposis (NP) is uncertain. Over a 4-yr period, we investigated the long-term changes of pulmonary function and BHR in 46 patients with NP. Each subject was assessed for nasal symptoms and tested for allergy skin prick tests, serum total IgE, spirometry, and carbachol challenge at baseline before initiating any treatment (T0). Nasal symptoms evaluation, spirometric measurements, and carbachol challenge were repeated at T1 and at T2 (respectively, 12.7 +/- 0.9 and 47.9 +/- 2. 2 mo after T0). In addition, bronchodilator response was measured at T2. At T0, 25 patients exhibited BHR and 16 of 25 were asthmatic. All patients were treated first with topical steroids for 6 wk (beclomethasone 600 microg/d). Eighteen patients were successfully treated with topical steroids (topical steroids responders). Intranasal ethmoidectomy was performed in 28 patients who did not improve with topical steroids alone (topical steroids nonresponders). Nasal score improved at T1 and remained improved at T2 as compared with T0 in both groups (p < 0.005). Topical steroids nonresponders demonstrated a significant decrease of FEV(1), FEV(1)/FVC ratio, and FEF(25-75) at T1 (p < 0.05) and at T2 (p < 0.0005), whereas no significant change was observed in FEV(1) and FEV(1)/FVC ratio in responders. DeltaFEV(1) (%) between T2 and T0 was not related to the presence of asthma, BHR, or atopy. Bronchodilator response at T2 was similar in the two groups. BHR did not significantly change over the 4-yr follow-up period in the two groups. No change in pulmonary symptoms and/or asthma severity occurred. Our results show that nonreversible airflow obstruction appears over a 4-yr follow-up period in topical steroids nonresponders patients with NP requiring nasal surgery. The long-term contribution of these changes to the development of respiratory symptoms in patients with NP remains to be documented.

Administration, Intranasal↗
PubMed2000

CC chemokines and interleukin-5 in bronchial lavage fluid from patients with status asthmaticus. Potential implication in eosinophil recruitment.

In status asthmaticus (SA), severe bronchial inflammation is associated with acute respiratory failure. Neutrophils are the prominent cells found in bronchi from SA patients, but eosinophils are also recruited within the first 48 h after the beginning of mechanical ventilation (MV). Interleukin (IL)-5 and CC chemokines have been directly implicated in the pathophysiology of allergic asthma. However, their involvement in SA had not been determined. The aim of this study was to evaluate the production of CC chemokines and of IL-5 in airways from ventilated patients with SA as compared with mild asthma (A), and to assess the role of these mediators in eosinophil recruitment. We measured levels of the chemokines monocyte chemotactic proteins (MCPs)-1 and -3; regulated on activation, normal T-cell expressed and secreted (RANTES); macrophage inflammatory peptide (MIP)-1alpha; and eotaxin; and of the cytokine IL-5 in bronchial lavage fluid (BLF) from 10 SA patients, four patients without respiratory disease but undergoing ventilation (V) who were receiving MV, 11 patients with A, and eight healthy volunteers (C). We further evaluated in vitro eosinophil chemotactic activity of BLF from the various groups. Levels of MCP-1, MIP-1alpha, RANTES, and IL-5 were significantly higher in the SA than in the V, A, and C groups. MCP-3 and eotaxin values were not significantly different in the SA and other groups; however, their levels, as well as those of MIP-1alpha, RANTES, and IL-5 correlated with eosinophil influx. Eosinophil chemotactic activity in BLF was increased in asthmatic subjects (A and SA groups) as compared with the other groups, and in SA patients as compared with A patients. Addition of neutralizing anti-IL-5, anti-MCP-3, anti-eotaxin, and anti-RANTES antibodies significantly inhibited the eosinophil chemotactic activity as compared with that of native BLF. This study shows that the levels of various CC chemokines and IL-5 are increased in airways of SA patients, and are potentially involved in eosinophil recruitment.

Adult↗
PubMed2000

Synergistic effect of diesel organic extracts and allergen Der p 1 on the release of chemokines by peripheral blood mononuclear cells from allergic subjects: involvement of the map kinase pathway.

The organic compounds of diesel exhaust particles (DEP-PAHs) have been shown to favor immunoglobulin production and bronchial hyperresponsiveness and to affect cytokine and chemokine productions. To evaluate if diesel exhaust could act in synergy with a house dust mite allergen (Der p 1), peripheral blood mononuclear cells from allergic patients were exposed to DEP-PAHs, with or without purified Der p 1. DEP-PAHs and Der p 1 separately induced an increase in interleukin (IL)-8, regulated on activation, normal T cells expressed and secreted (RANTES), and tumor necrosis factor-alpha concentrations. Interestingly, a synergy between the two stimuli was also observed. In the case of monocyte chemotactic protein (MCP)-1, DEP-PAHs reduced the release, whereas Der p 1 enhanced it. A simultaneous exposure led to reduced production as compared with allergen exposure alone, but still represented an increase as compared with the control exposure. Mitogen-activated protein (MAP) kinase Erk1/2 antagonist mainly inhibited the release of MCP-1, whereas MAP kinase p38 antagonist mainly suppressed the release of IL-8 and RANTES. Messenger RNA expression correlated with protein measurements. Moreover, supernatants from cells exposed to both DEP-PAHs and Der p 1 had a significant chemotactic activity on neutrophils and eosinophils. These findings suggest that simultaneous exposure of allergic patients to DEPs and allergens could result in high local chemokine levels via MAP kinase pathways activation, increasing the likelihood of reaching a critical threshold leading to the initiation of respiratory allergic symptoms.

Antigens, Dermatophagoides↗
PubMed2000

[Allergic bronchopulmonary aspergillosis].

Allergic bronchopulmonary aspergillosis (ABPA) is an immunologic bronchopulmonary inflammation due to an immune response of the lower respiratory tract against Aspergillus fumigatus. The major clinical features of ABPA include asthma, recurrent pulmonary infiltrates, immediate wheal and flare skin reactivity to A. fumigatus, elevated total serum IgE levels, detectable serum precipitating antibodies to A. fumigatus, peripheral blood eosinophilia, elevated levels of Aspergillus-specific serum IgE and central bronchiectasis with normal distal structures. The diagnosis of ABPA should be considered in asthmatics of all ages. Evolution of the disease comprises five stages from the acute to the fibrotic stage including pulmonary fibrosis and respiratory insufficiency. The goals of ABPA treatment are to control patient's asthma and prevent exacerbations of ABPA. During the acute stage, prednisone should be administered. Antifungals agents (itraconazole) may be useful to prevent exacerbations of the disease.

Aspergillosis, Allergic Bronchopulmonary↗
PubMed2000

[Adult care centers for patients with cystic fibrosis: prerequisites and practical organization. Cystic Fibrosis Care Centers of Rennes and Lille].

In the past 40 years there has been an increase in the median age of survival of patients with cystic fibrosis (CF), attributed to advances in the diagnosis and treatment of patients with this disease. This progress was also due to the level of care provided by pediatricians and now by adult physicians in CF care centers. They centralize and integrate knowledge and skills of pulmonary medicine, gastroenterology, nutrition, nursing, respiratory therapy, social work, and genetics to provide specialized care to patients with CF from childhood to adulthood. They are also expected to develop teaching and research, particularly the development of new life-extending therapies. The continuity of care of this multisystemic disease is best carried out through a close collaboration between the patient's primary care physician or pulmonologist and the specialized staff of the CF care center.

Adult↗
PubMed2000

[Clinical manifestations and therapeutic approach in neurosarcoidosis].

Neurological impairment is a frequent cause of morbidity and mortality in patients with sarcoidosis. The aim of this study was to evaluate the clinical manifestations of the disease, the response to corticosteroids and alternative treatments. During a 5 year period, diagnosis of neurosarcoidosis was performed in 40 patients. We retrospectively analyzed clinical, laboratory data and response to treatments. Mean age was 41.3 years (range 17-72). Mean time of follow-up was 46 months. Neurologic signs were the first symptom in 50 p. 100 of cases and an isolated manifestation in 12.5 p. 100. Central nervous system impairment was seen in 60.7 p. 100, meningitis in 27 p. 100. Other clinical manifestations were cranial nerve palsies (27 p. 100), peripheral neuropathy (33 p. 100), myopathy (16 p. 100). Eighty percent of the patients were treated by corticosteroids. Because of a lack of efficacy 40 p. 100 of patient required alternative treatment (including methotrexate, cyclophosphamide, azathioprin, cyclosporin). Complete recovery was observed in only 27.5 p. 100 of cases confirming the severity of neurosarcoidosis. Forty percent of patients were clinically stable and 10 p. 100 worsened. No patient died. This study confirms that intensive initial treatment is often necessary to prevent irreversible lesions. Alternative treatment should be rapidly initiated in resistant forms.

Adolescent↗
PubMed2000

[The common mucosal immune system in respiratory disease].

The principal function of the mucosal immune system is to protect the mucosa from exogenous aggression. It also involves a lymphocyte recirculation phenomenon allowing activated lymphocytes to migrate to the aggressed site, for example the bronchi, and to recirculate and colonize other sites of the mucosal immune system. In asthma, analysis of the other sites of the common mucosal immune system demonstrates asthma-like inflammatory reactions in the accessory salivary glands and the gut: lymphocyte infiltrate, mast cell activation, thickening of the basal membrane, accumulation and activation of eosinophils (gut), activation of endothelial cells expressing ICAM-1. Lymphocyte, eosinophil and mast cell infiltration is observed in the digestive tract as well as increased expression of IL-3, IL-5 and GM-CSF. The similarity of the anomalies observed in BALT and GALT tissues would suggest the entire mucosal immune system is implicated in asthma.

Asthma↗
PubMed1999

Quality of life in nasal polyposis.

BACKGROUND: Nasal polyposis (NP) is a frequent inflammatory chronic disease of the upper respiratory tract, which may impair quality of life (QOL). The NP impact, which is frequently associated with lower respiratory disorders, has never before been studied. OBJECTIVE: We initiated this prospective study to establish internal validity and reliability of the generic SF-36 questionnaire in NP and to determine to what level daily functioning becomes impaired as a result of NP. METHODS: Forty-nine consecutive patients with NP were included. They were assessed for the severity of nasal symptoms and underwent pulmonary function tests. The QOL profiles in patients with NP were compared with those of patients with perennial rhinitis (n = 111) and healthy subjects (n = 116). RESULTS: Cronbach's coefficient alpha demonstrated the high reliability and validity of the SF-36 questionnaire for patients with NP (alpha =.89). NP impaired QOL more than perennial allergic rhinitis (P <.05). The impairment of QOL was greater when NP was associated with asthma (P <.05). SF-36 scores appeared highly correlated to pulmonary function (FEV1, maximal midexpiratory flow, forced vital capacity), suggesting relationships between QOL in NP and associated bronchial obstruction. Severity of nasal symptoms were not related to QOL scales. In addition, sequential evaluations of QOL, nasal symptoms, and pulmonary function were performed 10 months after the first evaluation in 28 patients with NP. These evaluations demonstrated that NP treatment either with nasal steroids or endonasal ethmoidectomy significantly improved both nasal symptoms and QOL without significant change of pulmonary function. CONCLUSION: Our study clearly demonstrated that the SF-36 questionnaire presented a high internal validity and reliability in patients with NP. NP impaired QOL to a greater degree than perennial allergic rhinitis. QOL improvement after NP treatment is related to nasal symptoms improvement.

Adult↗
PubMed1999

Eosinophilic airway inflammation in nasal polyposis.

BACKGROUND: Asthma and asymptomatic bronchial hyperresponsiveness (BHR) are frequent findings in patients with nasal polyposis (NP). OBJECTIVE: To elucidate mechanisms responsible for the development of BHR, we initiated a prospective study of bronchial inflammation as assessed by bronchial lavage (BL) and bronchial biopsy specimens in 35 patients with noninfectious NP. METHODS: BHR was determined with methacholine provocation testing. Differential cell count, ECP, and histamine and tryptase levels were determined in BLs. Pathologic examination of bronchial biopsy specimens was performed with May-Grünwald-Giemsa stain to assess the number of lymphocytes. Indirect immunoenzymatic methods were used to identify eosinophils and mast cells. RESULTS: Fourteen patients did not exhibit BHR (group A); 7 patients had asymptomatic BHR (group B); and 14 patients had BHR associated with asthma (group C). Patients of group C tended to have a longer duration of nasal symptoms than those of groups A and B. FEV1 (L) was significantly lower in group C than in groups A and B. The number and percentage of eosinophils were significantly higher in BLs in groups B and C than in group A (P <. 05). Patients of groups B and C had a significantly higher number of eosinophils in bronchial submucosa (14.0 +/- 1.5/mm2 and 19.0 +/- 1. 9/mm2, respectively) than patients of group A (0.1 +/- 0.1/mm2). The number of lymphocytes was also higher in groups B and C than in group A. FEV1 (percent of predicted value) and eosinophil number within bronchial mucosa correlated negatively. CONCLUSION: Our results demonstrate that patients with NP and asymptomatic BHR had an eosinophilic bronchial inflammation similar to that observed in asthmatic patients with NP, whereas patients with NP without BHR do not feature eosinophilic lower airways inflammation. The clinical relevance of these results requires careful follow-up to determine whether eosinophilic inflammation in these patients precedes and is responsible for the development of obvious asthma.

Adult↗
PubMed1999

Effects of diesel organic extracts on chemokine production by peripheral blood mononuclear cells.

BACKGROUND: Polyaromatic hydrocarbons (PAHs) associated with diesel exhaust particles (DEPs) are found in the atmospheric urban pollution. Such compounds have been shown to favor IgE production, bronchial hyperresponsiveness, and airway inflammation. Chemokines are a group of chemotactic cytokines involved in the recruitment of inflammatory cells. OBJECTIVE: We investigated the effect of DEP-PAHs on the release and mRNA expression of IL-8, MCP-1, and RANTES by PBMCs obtained from healthy subjects. METHODS: Protein production in supernatants was assessed by ELISA, and mRNA expression was evaluated by semiquantitative RT-PCR. RESULTS: Secretion of IL-8 and RANTES increased in a dose-dependent manner with increasing concentrations of DEP-PAHs (range, 0.5 ng to 50 ng/mL). On the contrary, the release of MCP-1 was significantly inhibited, also in a dose-dependent manner. Messenger RNA production coding for IL-8, RANTES, and MCP-1 showed parallel variations to the production of the correspondent proteins. Effects of DEP-PAHs became significant at 7 hours and up to 48 hours time culture for MCP-1, and up to 24 hours time culture for IL-8 and RANTES. Moreover, supernatants from DEP-PAH-activated cells, compared with those of controls, exhibited a significantly enhanced chemotactic activity for neutrophils and eosinophils, which was significantly inhibited by pretreatment with anti-IL-8 and anti-RANTES neutralizing antibodies, respectively. CONCLUSION: These findings suggest that the chemokine pathways are modulated by DEP-PAHs at the transcriptional level, reinforcing the idea that the development of inflammatory reactions might be affected by diesel exhaust emission.

Cell Survival↗
PubMed1999

Production of chemokines and proinflammatory and antiinflammatory cytokines by human alveolar macrophages activated by IgE receptors.

BACKGROUND: The alveolar macrophage (AM) expresses the low affinity IgE receptor and has the ability to produce not only several proinflammatory cytokines (TNF-alpha, IL-1, IL-6) but also antiinflammatory cytokines (IL-1 receptor antagonist [IL-lra], IL-10), chemokines (IL-8, monocyte chemotactic protein-1 [MCP-1]), and macrophage inflammatory protein-1alpha (MIP-1alpha). OBJECTIVE: The aim of this study was to evaluate the capacity of the AM from patients with allergic asthma and control subjects to produce chemokines and antiinflammatory versus proinflammatory cytokines after activation by IgE receptors and to define the role of CD23 in this activation. METHODS: AMs were collected by bronchoalveolar lavage from 13 patients with allergic asthma and 14 healthy subjects. Adherent AMs were activated either by the successive addition of IgE and anti-IgE or by monoclonal mouse IgG anti-CD23 or by a control monoclonal mouse antibody. TNF, IL-1beta, IL-1ra, IL-10, IL-8, MCP-1, and MIP-1alpha levels were evaluated in supernatants of AMs incubated for 18 hours and in some cases after 4 hours of incubation. RESULTS: Activation by IgE and anti-IgE antibodies significantly increased the production of TNF, IL-1beta, IL-8, MCP-1, MIP-lalpha, and IL-10 in both control subjects and patients with asthma, whereas the increase for IL-1ra was only significant for the control subjects. Whereas F(ab) fragments of anti-CD23 antibodies inhibited IgE plus anti-IgE-induced cytokine production, activation by monoclonal IgG anti-CD23 antibodies reproduced the effect of IgE immune complexes. At 4 hours, the secretion of proinflammatory cytokines was increased by activation by IgE receptors, in contrast to antiinflammatory cytokines. In addition, analysis of the balance between proinflammatory and antiinflammatory cytokines showed that IgE-dependent activation largely favored the proinflammatory cytokines, particularly in patients with asthma. CONCLUSION: IgE-dependent activation by the FcepsilonRII receptor upregulates the synthesis of both chemokines and antiinflammatory cytokines in addition to proinflammatory cytokines. However, AMs from patients with allergic asthma may promote airway inflammation after activation by IgE receptors through its preferential effect on proinflammatory cytokines.

Animals↗
PubMed1999

A comparison of two long-acting beta-agonists, oral bambuterol and inhaled salmeterol, in the treatment of moderate to severe asthmatic patients with nocturnal symptoms. The French Bambuterol Study Group.

This multicentre study was set up to compare the efficacies of two long-acting beta 2-agonists, oral bambuterol (20 mg nocte) and inhaled salmeterol (50 micrograms b.i.d.), for the treatment of moderate to severe asthmatics who were considered to be on optimal steroid/bronchodilator therapy, but continued to have troublesome nocturnal symptoms. The study was of double-blind, parallel-group design and comprised a 2-week run-in on previous maintenance therapy followed by a 6-week study treatment period. There were 117 randomized asthmatic patients aged 20-70 years (65 women and 52 men with a mean age of 45 and predicted FEV1 of 64%), who had been taking 800-2000 micrograms inhaled steroid and/or up to 20 mg oral steroid per day for at least 4 weeks. They were asked to complete daily diary cards, recording morning and evening PEF, daily symptoms, nocturnal awakenings, rescue medication and subjective tremor. There was a significant increase in both morning and evening PEF respectively, on bambuterol (28 l min-1, 20 l min-1, P < 0.05) and salmeterol (29 l min-1, P < 0.001; 23 l min-1, P < 0.01) when compared with run-in. The mean percentage fall in overnight PEF was reduced by 8.3% (P < 0.001) on bambuterol and by 6.8% (P < 0.001) on salmeterol. Nocturnal awakenings and daytime symptoms due to asthma were significantly lowered by both treatments, as was the consumption of rescue bronchodilator. Tremor scores were very low during both run-in and study treatments. No significant treatment difference between bambuterol and salmeterol was detected for any of the above variables. Once-daily oral bambuterol provides a highly effective alternative to twice-daily inhaled salmeterol for relief of nocturnal symptoms in patients with moderate to severe asthma.

Administration, Inhalation↗
PubMed1999

Thiol regulation of the production of TNF-alpha, IL-6 and IL-8 by human alveolar macrophages.

Reactive oxygen intermediates exert signalling functions and modulate gene transcription, particularly for pro-inflammatory cytokines. Since exogenous as well as endogenous thiols could be potent inhibitors of the production of cytokines, the effects of N-acetylcysteine (NAC), glutathione (GSH) and modulated GSH synthesis on the production of tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-8 by human alveolar macrophages (AMs) was evaluated, as well as the potential role of intracellular GSH depletion on the effect of exogenous thiols. AMs were stimulated with lipopolysaccharide (LPS) and cytokine production was measured by evaluating messenger ribonucleic acid (mRNA) expression and protein secretion. Depletion of intracellular GSH by treatment with buthionine sulphoximine (BSO) reached 45.2% after 3 h and was nearly complete at 24 h. Whereas a 24-h preincubation of AMs with BSO significantly increased LPS-induced secretion of TNF-alpha and IL-8, a 3-h preincubation only enhanced LPS-stimulated production of IL-8 (p<0.05). Treatment with NAC and GSH did not significantly increase intracellular content of GSH even after a 48-h incubation. Addition of GSH and NAC significantly reduced the secretion of TNF-alpha (mean+/-SEM 21.2+/-5 and 44.7+/-4.4% inhibition, respectively) as well as LPS-induced IL-6 and IL-8 (p<0.05). Similarly, NAC inhibited the production of TNF-alpha, IL-6 and IL-8 in GSH-depleted AMs obtained by BSO pretreatment. In conclusion, N-acetylcysteine and glutathione inhibit the production of tumour necrosis factor-alpha, interleukin-8 and interleukin-6 by alveolar macrophages by a mechanism independent of glutathione metabolism. However, total depletion of glutathione within alveolar macrophages significantly increases tumour necrosis factor-alpha and interleukin-8 synthesis whereas it does not modulate interleukin-6 secretion.

Acetylcysteine↗
PubMed1999

Airway epithelium expresses interleukin-18.

Interleukin (IL)-18 is an interferon (IFN)-gamma-inducing cytokine suggested to be important in regulating inflammatory responses. This study investigated the pulmonary expression of IL-18 under conditions characterized by T-helper (Th)1 (lipopolysaccharide (LPS) treatment/sarcoidosis) and Th2 (ovalbumin (OVA) challenge/asthma) cytokine production. In situ hybridization and immunocytochemistry were used to determine the number of cells expressing IL-18, IFN-gamma, IL-5 and major basic protein (MBP) within lung tissue from Balb/c mice stimulated with LPS, OVA and in normal control mice. Bronchial biopsies from patients with sarcoidosis, asthma and control individuals were also examined. IL-18 was localized primarily to airway epithelium and mononuclear cells. Constitutive expression was observed within the lungs of control mice. Animals challenged with LPS exhibited more IL-18 messenger ribonucleic acid (mRNA)-positive and IFN-gamma immunoreactive cells, compared to control mice (p<0.01). OVA-challenged mice had fewer IL-18 mRNA positive and more IL-5 and MBP immunoreactive cells, compared to control mice (p<0.01). Similarly, constitutive expression of IL-18 protein was observed within the airway epithelium of control individuals, with more positive cells found within sarcoidosis tissue (p<0.01) and fewer within asthmatic tissue (p<0.01), compared to controls. These results demonstrate the expression of interleukin-18 within airway epithelium and the regulation of this cytokine under conditions of both T-helper1 and T-helper2 cytokine production.

Adult↗
PubMed1999

Interleukin-5 immunoreactivity and mRNA expression in gut mucosa from patients with food allergy.

BACKGROUND AND AIMS: Eosinophils, mast cells and T lymphocytes are important cells in the allergic inflammatory process. These cells produce and are regulated by cytokines such as interleukin-3 (IL-3), interleukin-5 (IL-5) and granulocyte macrophage-colony stimulating factor (GM-CSF). We initiated this study to evaluate pathological abnormalities and to detect IL-5 in the duodenal mucosa from patients with food allergy. METHODS: Endoscopy duodenal biopsy specimens were obtained from seven food-allergic patients, six atopic healthy controls and six nonatopic healthy controls. IL-5 protein was evaluated by immunohistochemistry. Electron microscopy as well as double immunofluorescent staining were used to identify the labelled cells and to localize IL-5. IL-5 mRNA expression was evaluated by qualitative polymerase chain reaction. RESULTS: A significantly increased number of lymphocytes, mast cells and eosinophils was detected in the lamina propria in food-allergic patients and, in lower number, in atopic controls. Immunostaining for IL-5 was markedly positive in food-allergic patients, slightly increased in atopic controls and negative in nonatopic controls. Ultrastructurally, in food-allergic patients and in atopic controls, IL-5 was localized in eosinophil granules, in the matrix of intact granules and at the periphery of altered granules. Double immunofluorescent staining was performed in food-allergic patients and showed that 86.7% of IL-5+ cells were eosinophils, and that IL-5 was expressed by 24% of eosinophils. IL-5 mRNA was expressed in food-allergic patients but was not detected in atopic and nonatopic controls. CONCLUSION: Activated eosinophils are involved in gut atopic reactions occurring in food allergy and are probably in part upregulated by their own local production of IL-5.

Adolescent↗