ABSTRACT
Chemokines are cytokines with chemotactic properties on leukocyte subsets whose modulation plays a key role in allergic inflammatory processes. To better understand the possible anti-inflammatory effects of histamine-1 receptor antagonists in allergic asthma, we studied the mRNA expression of a set of chemokines known to be involved in the eosinophils-basophils activation as well as recruitment and T-cell signaling events, before and after corticosteroid or antihistamine treatment in PBMCs from allergic-asthmatic patients ex vivo. Twelve patients were enrolled, all of whom were allergic to Parietaria judaica and suffering for mild persistent asthma: six were treated with desloratadine (10 mg/day), and six with deflazacort (12 mg/day). Before and after the treatment, PBMC samples were collected from each patient and analyzed for the expression of encoding mRNAs for several chemokines, I-309 (CCL1), MCP-1 (CCL2), MIP1-alpha (CCL3), MIP1-beta (CCL4), RANTES (CCL5), IL-8 (CXCL8), IP-10 (CXCL10), Lymphotactin (XCL1). Clinical and functional improvements were seen after 3 weeks of therapy; this was associated with a reduced expression in the mRNA levels for the chemokines RANTES, MIP1-alpha and MIP1-beta with either the corticosteroid or the antihistamine, compared to the pre-treatment levels. Chemokine downregulation was statistically significant in both groups of patients. These findings suggest that certain antihistamines may act as down-modulators of allergic inflammation, possibly through a negative regulation of the chemokines involved in activation and attraction of eosinophils. Our results suggest that clinical trials with long follow-ups may be useful in evaluating histamine-1 receptor antagonists as add-on therapy to steroids in the treatment of asthma.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Chemokines/biosynthesis , Eosinophils/drug effects , Histamine H1 Antagonists/pharmacology , Hypersensitivity/metabolism , Loratadine/analogs & derivatives , Monocytes/drug effects , Monocytes/metabolism , Pregnenediones/pharmacology , Adolescent , Adult , Albuterol/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Asthma/physiopathology , Bronchodilator Agents/therapeutic use , Cell Separation , Densitometry , Down-Regulation/drug effects , Female , Gene Expression/drug effects , Histamine H1 Antagonists/therapeutic use , Humans , Hypersensitivity/drug therapy , Loratadine/pharmacology , Loratadine/therapeutic use , Male , Nuclease Protection Assays , Parietaria/immunology , Pollen/immunology , Pregnenediones/therapeutic use , Respiratory Function Tests , Rhinitis, Allergic, Seasonal/metabolismABSTRACT
Seven women and eight men, exposed to low frequency (50 Hz) electromagnetic fields (EMFs) in a museum for 20 hours a week, were investigated in the years 1999 and 2005. During the first study, the mean EMF exposure in the working place was 1.7 microT and 1.1 microT, respectively. In the first investigation, the EMF-exposed men showed reduced blood NK lymphocytes in relation to controls, while EMF-exposed women presented reduced PHA-stimulated IFN-gamma release from peripheral blood mononuclear cells (PBMC). In the year 2005, blood cytotoxic activity, state and trait anxiety (STAI I and II, respectively) and occupational stress were also investigated. The scores of STAI I and II of the control women were slightly higher than those of the control men. EMF-exposed men showed higher occupational stress but normal immune parameters. EMF-exposed women showed, in relation to controls, lower PHA-stimulated IFN-gamma release from PBMC and reduced blood cytotoxic activity/CD45+-CD16+-56+ NK lymphocytes (but not per ml of blood). One of the women exposed to EMF, who worked a night shift, showed marked lymphopenia with very low NK lymphocytes and reduced IFN-gamma release; these immune parameters returned to normal following a change of work site. This study suggests that low frequency EMFs affect the immune functions of women more than those of men. Moreover, the determination of immune parameters seems to be a useful marker of the health effects of exposure to EMFs.
Subject(s)
Electromagnetic Fields/adverse effects , Immunity/radiation effects , Museums , Occupational Exposure/adverse effects , Adult , Female , Follow-Up Studies , Humans , Interferon-gamma/biosynthesis , Killer Cells, Natural/immunology , Killer Cells, Natural/radiation effects , Male , Middle Aged , Sex Characteristics , Stress, Psychological/etiologyABSTRACT
The object of this study was to investigate the immune system of 19 women with a mean age of 35 years, for at least 2 years (mean = 13 years) exposed to electromagnetic fields (ELMFs) induced by radiotelevision broadcasting stations in their residential area. In September 1999, the ELMFs (with range 500 KHz-3 GHz) in the balconies of the homes of the women were (mean +/- S.D.) 4.3 +/- 1.4 V/m. Forty-seven women of similar age, smoking habits and atopy composed the control group, with a nearby resident ELMF exposure of < 1.8 V/m. Blood lead and urinary trans-trans muconic acid (a metabolite of benzene), markers of exposure to urban traffic, were higher in the control women. The ELMF exposed group showed a statistically significant reduction of blood NK CD16+-CD56+, cytotoxic CD3(-)-CD8+, B and NK activated CD3(-)-HLA-DR+ and CD3(-)-CD25+ lymphocytes. 'In vitro' production of IL-2 and interferon-gamma (INF-gamma) by peripheral blood mononuclear cells (PBMC) of the ELMF exposed group, incubated either with or without phytohaemoagglutinin (PHA), was significantly lower; the 'in vitro' production of IL-2 was significantly correlated with blood CD16+-CD56+ lymphocytes. The stimulation index (S.I.) of blastogenesis (ratio between cell proliferation with and without PHA) of PBMC of ELMF exposed women was lower than that of the control subjects. The S.I. of blastogenesis of the ELMF exposed group (but not blood NK lymphocytes and the 'in vitro' production of IL-2 and INF-gamma by PBMC) was significantly correlated with the ELMF levels. Blood lead and urinary trans-trans muconic acid were barely correlated with immune parameters: the urinary metabolite of benzene of the control group was only correlated with CD16+-CD56+ cells indicating a slight effect of traffic on the immune system. In conclusion, this study demonstrates that high frequency ELMFs reduce cytotoxic activity in the peripheral blood of women without a dose-response effect.
Subject(s)
Antibody Formation , Electromagnetic Fields/adverse effects , Immunity, Cellular , Receptors, G-Protein-Coupled , Adult , Cytokines/analysis , Environmental Exposure , Female , Humans , Lymphocyte Activation/drug effects , Lymphocytes/immunology , Middle Aged , Public Health , Receptors, Cell Surface , Receptors, Ghrelin , Vehicle Emissions/adverse effectsABSTRACT
The objective of this study was to analyse the immune response to electromagnetic fields (ELMFs) in seven men and eight women employed in a museum. The workers were exposed in a room to an ELMFs (range 0.2-3.6 microT and 40-120 V/m) induced by 50 Hz electricity for 20 h a week. Control groups consisted of 47 women and 39 men with a similar percentage of atopic subjects, age (range 30-51 years) and smoking habits of the workers included in the study. Levels of blood lead (Pb) and urinary trans-trans muconic acid, a metabolite of benzene (markers of exposure to traffic and smoking) of the control and exposed groups were similar. Lymphocyte subsets were determined in men and women using conjugated antibodies. Serum interleukin (IL) 4 and interferon gamma and their 'in vitro' production by peripheral mononuclear blood cells (PMBCs) stimulated by phytohemoglutinin (PHA), as well as blastogenesis of PMBCs induced by PHA, were determined in women only. ELMF-exposed women showed a significant reduction in the percentage of B and NK CD3(-)-CD25+ lymphocytes and a slight reduction of CD16(+)-56+ NK lymphocytes. They also showed significantly lower levels of interferon gamma in serum, or produced in the supernatants by PMBCs both spontaneously and stimulated by PHA, while they did not show significant changes in serum and 'in vitro' produced IL-4, or in blastogenesis of PMBCs. Men working in the museum showed, in relation to the controls, a statistically significant reduction in both number and percentage of CD16(+)- CD56+ and CD3(-)-CD25+ lymphocyte subsets. On the whole, this investigation demonstrates a reduction of blood NK lymphocytes and of the production of interferon gamma in workers exposed to low frequency ELMFs. Recent studies have shown that stress and poor lifestyle induce the reduction of blood cytotoxic activities possibly acting on nervous functions. This may suggest that ELMFs reduces blood NK lymphocytes by combined effects on the immune and nervous systems.
Subject(s)
Cytokines/metabolism , Electromagnetic Fields/adverse effects , Lymphocyte Subsets/physiology , Museums , Sorbic Acid/analogs & derivatives , Adult , Case-Control Studies , Cells, Cultured , Female , Humans , Immunoglobulin E/blood , Interferon-gamma/blood , Interleukin-4/blood , Lead/blood , Male , Middle Aged , Neutrophils/metabolism , Occupational Exposure , Sorbic Acid/analysisABSTRACT
The aim of the study was to assess the seasonal variability of non-specific bronchial reactivity (NSBR) evaluated with methacholine in asthmatic farmers allergic to pollens. Twenty farmers (16 male and four female) with allergy to pollens, e.g. 'Graminae' and 'Parietaria', entered the study. None of the patients had been previously treated with specific immunotherapy. Patients underwent a methacholine challenge at the first visit and then in the subsequent seasons. Four groups of tests were obtained according to the period when the challenge was performed. Group 1: challenges performed in December, January and February; group 2 in March, April and May; group 3 in June, July and August; group 4 in September, October and November. PD20 values were expressed as the natural logarithm of the cumulative dose of methacholine causing at least a 20% fall in FEV1. Bronchial hyperreactivity was highest in summer, followed by spring and autumn; in winter it was much lower. Multiple group analysis (ANOVA) showed statistically significant differences between the groups (P < 0.01). When the groups were compared individually, statistically significant differences existed only between group 1 (winter) and each of the other groups, respectively 2 (spring) (P = 0.02), 3 (summer) (P = 0.004) and 4 (autumn) (P = 0.02). The results underlined the importance of allergic inflammation in determining changes in NSBR. In the region where the study was carried out (central Italy), the grass and Paretaria pollination lasts from March to November. Therefore, farmers had a progressive increase in NSBR from spring to summer and a decrease in fall as a consequence of the varying pollen concentration in different seasons. The level of allergen exposure is, in fact, the main factor that determines the severity of bronchial inflammation, thus affecting NSBR.
Subject(s)
Agriculture , Allergens , Asthma/immunology , Bronchial Provocation Tests , Female , Humans , Italy , Male , Pollen , SeasonsABSTRACT
The aim of the study was to assess the seasonal variability of non-specific bronchial responsiveness to methacholine in allergic asthma. One hundred sixty-five patients (83 male and 82 female) entered the study: 86 subjects (group A) with allergy exclusively to mites and 79 (group B) with concomitant allergy to pollens, e.g., "Graminae" and "Parietaria." Inclusion criteria were the absence of sensitization to other allergens, no smoking habit, withdrawal from steroids, bronchodilators, sodium cromoglycate, and antihistamines for at least four weeks before enrollment, FEV1 > 70% of the predicted value, and absence of other respiratory diseases and of upper and lower respiratory tract infections for at least one month before the methacholine challenge. None of the patients had been previously treated with specific immunotherapy. Subjects of each group (A and B) underwent methacholine challenge at first visit and were divided into four subgroups according to the period when the challenge was performed. Subgroups A1 and B1 performed the challenge in December, January, and February; subgroups A2 and B2 in March, April, and May; subgroups A3 and B3 in June, July, and August; subgroups A4 and B4 in September, October, and November. PD20 values were expressed as the natural logs of the cumulative dose of methacholine causing at least a 20% fall in FEV1. Statistical analysis was carried out using multiple group analysis and Student's t-test. Results showed that the highest non-specific bronchial responsiveness was observed in autumn (ln PC20 = 4.54 +/- 1.51) in patients allergic to mites only (group A), and in summer (ln PC20 = 4.72 +/- 2.11) in those of group B. Multiple group analysis showed statistical significant differences between subgroups within each group (group A, p = 0.039; group B, p < 0.001). In patients allergic exclusively to house dust mites (group A), multiple comparisons and Student's t-test showed statistically significant differences between non-specific bronchial responsiveness (NSBR) assessed in autumn and those of other seasons (winter, p = 0.002; spring, p < 0.001; summer, p = 0.082). These results confirm that the level of allergen exposure may influence NSBR. Mite-allergic patients showed an increase of NSBR in autumn, possibly as a consequence of higher indoor mite concentration. However, mite- and grass-allergic patients had wider variations of NSBR, possibly reflecting changes in seasonal pollen concentration.
Subject(s)
Asthma/physiopathology , Bronchial Hyperreactivity , Dust/adverse effects , Glycoproteins/immunology , Hypersensitivity, Immediate/etiology , Adolescent , Adult , Allergens/immunology , Animals , Antigens, Dermatophagoides , Bronchial Provocation Tests , Child , Female , Forced Expiratory Volume , Housing , Humans , Male , Methacholine Chloride/pharmacology , Mites/immunology , SeasonsABSTRACT
BACKGROUND: The responses to airway hyperosmolar challenges probably involve various inflammatory mediators. However, it is not fully understood which cell type/types are the source of these mediators. Potential cell types include mast cell, epithelial cell and the sensory c-fibre nerve cell. OBJECTIVE: To clarify which cell types are involved with the mediator response to hyperosmolarity in the human airway. METHODS: Ten healthy subjects, 11 patients with nonactive allergic rhinitis, and nine with active allergic rhinitis were challenged intranasally with mannitol powder, and with sham provocation, on separate days. Symptoms were assessed by visual analogue scales and nasal patency by measuring the nasal peak inspiratory flow (nPIF). Nasal lavage fluid levels of alpha(2)-macroglobulin (an index of plasma extravasation), substance P (an index of sensory nerve cell activation), tryptase (an index of mast cell activation) and 15-hydroxyeicosatetraenoic acid (15-HETE, an index of epithelial cell activation) were analysed. RESULTS: Immediate, although transient burning was the most prominent symptom in all groups whereas only the patients with active rhinitis experienced a fall in nPIF. Mannitol significantly increased the nasal lavage fluid 15-HETE levels in the allergic patients (P < 0.01 vs the sham challenge), but not in the healthy subjects. The increase in 15-HETE correlated with nasal symptoms for itching (r(s) = 0.65, P = 0.019) and burning (r(s) = 0.72, P = 0.009). Detectable levels of tryptase was found only in five allergic subjects. Lavage levels of substance P and alpha(2)-macroglobulin did not not change. CONCLUSION: Epithelial cell seems to be involved with the mediator response to airway hyperosmolar challenge. The roles of sensory c-fibre nerve cell and mast cell remained less clear.
Subject(s)
Hypertonic Solutions/administration & dosage , Mannitol/administration & dosage , Nasal Mucosa/immunology , Rhinitis, Allergic, Perennial/immunology , Adult , Epithelial Cells/drug effects , Epithelial Cells/immunology , Female , Humans , Hydroxyeicosatetraenoic Acids/metabolism , Inspiratory Capacity , Male , Mast Cells/immunology , Nasal Lavage Fluid/immunology , Nasal Mucosa/drug effects , Nasal Provocation Tests , Nerve Fibers/immunology , Powders , Rhinitis, Allergic, Perennial/physiopathology , Serine Endopeptidases/metabolism , Sneezing , Spirometry , Substance P/metabolism , Tryptases , alpha-Macroglobulins/metabolismABSTRACT
This study evaluates the immune response to exposure to an urban environment from 30 non-atopic and 30 non-symptomatic women with history of respiratory and/or cutaneous allergies. Blood lymphocyte subsets and serum interleukin (IL) 4 and interferon gamma (INF-gamma) of the two groups were similar, while serum IgE and "in vitro" production of IL-4 and INF-gamma by mononuclear blood cells of the atopic women were higher spontaneously or in the presence of PHA, respectively. Blood lead of the nonatopic women (mean 55 microg/l) was positively correlated with CD4+-CD45RO-, CD3+-CD8+ and CD3--HLA-DR+ lymphocyte subsets, while urinary trans-trans muconic acid (a metabolite of benzene) of both groups of women (mean about 50 microg/l) was significantly correlated with NK CD16+CD56+ lymphocytes. Urine chromium of the non-atopic subjects was significantly correlated with activated T, B and NK HLA-DR+ cells. Urine nickel of both groups of women was correlated with CD4+-CD45RO+ "memory" lymphocytes and their ratio with CD4+-CD45RO- "virgin" lymphocytes suggesting that the metal enhances maturation of "virgin" into "memory" lymphocytes. On the whole, this study demonstrates that exposure to low levels of toxic agents, produced by vehicular traffic in an urban environment, exerts effects on immune functions of women.
Subject(s)
Hypersensitivity, Immediate/immunology , Interferon-gamma/blood , Interleukin-4/blood , Lymphocyte Subsets/immunology , Sorbic Acid/analogs & derivatives , Trace Elements/blood , Trace Elements/urine , Urban Health , Adult , Chromium/urine , Cities , Copper/blood , Environmental Exposure , Female , Humans , Hypersensitivity, Immediate/blood , Hypersensitivity, Immediate/urine , Immunoglobulin E/blood , Immunologic Memory/immunology , Interferon-gamma/biosynthesis , Interleukin-4/biosynthesis , Lead/blood , Leukocytes, Mononuclear/metabolism , Lymphocytes/immunology , Middle Aged , Nickel/urine , Sorbic Acid/metabolism , Zinc/bloodABSTRACT
We assessed the infiltration of CD45RO+ cells in conjunctival biopsies of fifteen subjects affected by seasonal allergic conjunctivitis by means of immunohistochemistry. Correlations between infiltration of CD45RO+ cells and serum and mucosal indices of eosinophilic activation were investigated. The study was performed in autumn and all selected patients showed <
Subject(s)
Conjunctiva/pathology , Conjunctivitis, Allergic/immunology , Conjunctivitis, Allergic/pathology , Eosinophils/immunology , Leukocyte Common Antigens/analysis , Leukocytes/immunology , Ribonucleases , Adolescent , Adult , Biopsy , Blood Proteins/analysis , Chronic Disease , Conjunctiva/immunology , Conjunctivitis, Allergic/blood , Enzyme-Linked Immunosorbent Assay , Eosinophil Granule Proteins , Humans , Immunoglobulin E/blood , Immunohistochemistry , Mucous Membrane/immunology , Mucous Membrane/pathology , SeasonsABSTRACT
The aims of this study were to determine the incidence of toxoplasmosis in children ofthe northern Greece region through the evaluation of serologic examination. Sera of 486 children, aged between 6 months and 15 years, suffering from different clinical entities, were tested for anti-Toxoplasma gondii specific IgG antibodies, using an ELISA (enzyme linked immunosorbent assay) technique. In this survey, a high percentage (11.1 percent) of the hospitalized children reacted positively to this method. Males and females had equal prevalence, 11 percent and 11.2 percent, respectively. Seropositivity rate was higher in children aged between 6 and 10 years old. In conclusion, our results indicate toxoplasma infection is an important public health problem affecting children and adolescents in northern Greece. We believe that the study described here could be considered for inclusion in existing national screening programs for hospitalized children.
ABSTRACT
Allergen-specific immunotherapy (IT) consists in administering gradually increasing doses of an allergen extract to sensitive patients. This practice results in ameliorating symptoms associated with the subsequent exposure to the causative allergen. Presently, the lack of therapies which affect the pathogenesis of the disease make IT the only treatment that may improve the natural course of allergic diseases.