Chronic rhinosinusitis with nasal polyposis and biological agents: the ARIA-ITALY Survey.

Summary: Background. Chronic rhinosinusitis (CRS) is an inflammatory disease that affects the nasal mucosa and the paranasal sinuses. CRS can be associated by nasal polyposis (CRSwNP phenotype) in up to 30% of patients and it is frequently associated with bronchial asthma. CRSwNP shows predominantly an underlying activation of type 2 inflammatory pathways with the involvement of eosinophils, IgE, interleukin (IL)-4, IL-5 and IL-13. Biological drugs that target these inflammatory cytokines are currently a therapeutic option recognized by guidelines for the treatment of uncontrolled form of the disease. Methods. As part of the activity of the "ARIA-Italy" working group, a panel of 255 Italian Ear, Nose and Throat (ENT) specialists, pneumologists and immuno-allergologists actively participated in this national survey and answered a series of questions geared toward understanding the main criteria for patient characterization and therapeutic decision, highlighting multidisciplinarity, and the implementation of the management of CRSwNP patients, as a part of the precision medicine concept and the appropriate use of the biologicals. Results. Two hundred and fifty-five experts and specialists participated in the survey. Conclusions. The results of this survey obtained from an extensive number of active specialists throughout Italy allow some important concluding remarks to be drawn. The main points of agreement were that multidisciplinary care teams provide many benefits but that, once the team is established, meetings and communication between members must be coordinated. Finally, the dissemination of national disease registries and the continuous updating of guidelines and position papers related to CRSwNP and comorbidities should be encouraged.

Allergooncology: an expanding research area.

The relationship between allergic diseases and cancer is a very controversial topic, widely discussed in the last decades. Many studies have demonstrated inverse association between allergy and cancer, but others have reached neutral conclusions or have indicated a positive role of allergy in the development of cancer. However, either inhibiting or favoring, many cells and molecules relevant in the allergic process play a role in tumorigenesis. On the one hand, activated immune cells, like classically activated macrophages "M1", activated dendritic cells, IL-33 and amphiregulin stimulated Innate Lymphoid Cells (ILC2), Th1, IFN-γ producing T CD8+ and B lymphocytes have inhibitory effects on tumorigenesis and tumor progression. On the other hand, tolerogenic immune cells, like alternatively activated macrophages "M2" (M2a, M2b and M2c), tolerogenic dendritic cells, ILC3, T regulatory and B regulatory lymphocytes, while inhibiting allergic sensitization and response, appear to favour carcinogenesis. Furthermore, M2 subtypes macrophages (M2a, M2b), IL-25 stimulated ILC2 and Th2 lymphocytes have a role both in inducing allergic reactions and in favouring cancer progression. In addition, mast cells, pivotal cells in allergy, have a different effect of tumorigenesis based on their location - they can promote cancer progression or inhibit it. Finally, eosinophils have shown a prevalent tumoricidal function mediated by α-defensins, TNF-α, granzymes A and IL-18. Better understanding the role of various cells on carcinogenesis can help in developing new strategies (diagnostic, therapeutic and of follow up) against tumor.

The metallobiochemistry of ultratrace levels of platinum group elements in the rat.

The use of platinum, palladium and rhodium (Platinum Group Elements - PGEs) and the possibility of exposure to their ultratrace levels is increasing. In fact, the exponential development of metallic PGE-based nanoparticles (<100 nm in size) opens extraordinary perspectives in the areas of electrocatalysts and catalytic converters, magnetic nanopowders, polymer membranes, cancer therapy, coatings, plastics, nanofibres and textiles. Like other metal-based nanoparticles, exposure to PGEs nanoparticles may result in a release of ultratrace amounts of Pt, Pd, Rh ions in the body whose metabolic fate and toxicity still need to be evaluated. Furthermore, PGEs can act as allergic sensitizers by acting as haptens and inducing both type I and IV allergic reactions. In this work we studied the in vivo metabolic patterns of ultratrace levels of potent allergens and sensitizers PGE halogenated salts. (191)Pt, (103)Pd and (101m)Rh radioisotopes were prepared via cyclotron irradiation and used for radiolabelling Na2(191)PtCl4, Na2(103)PdCl4 and Na2(101m)RhCl6 salts. These anionic chlorocomplexes were intraperitoneally injected into rats (114 ng Pt kg(-1) bodyweight; 24 ng Pd kg(-1) b.w.; 16 ng Rh kg(-1) b.w.). At 16 h post-exposure, PGEs were poorly but significantly retained in all tissues analysed. Kidneys, spleen, adrenal gland, liver, pancreas and small intestine were the organs with the highest Pt, Pd, Rh concentrations. In the blood 30-35% of (103)Pd and (191)Pt and 10% of (101m)Rh were recovered in the plasma, mainly bound to albumin and to a less extent to transferrin. The hepatic and renal intracellular distribution showed the highest recovery of (191)Pt, (103)Pd and (101m)Rh in the nuclear fraction (liver) and in the cytosol (kidney). Chromatographic separation and ultrafiltration experiments on kidney and liver cytosols showed the strong ability of biochemical macromolecules to bind (191)Pt, (103)Pd and (101m)Rh, and being responsible for the retention of the three elements in the body. The link to macromolecules is the basis for the sensitizing capacity of PGEs.

Systemic nickel allergy syndrome: nosologic framework and usefulness of diet regimen for diagnosis.

Systemic (gastrointestinal and skin) reactions to ingestion of nickel rich foods in patients with nickel allergic contact dermatitis characterize Systemic Nickel Allergy Syndrome (SNAS). The objective of the study was to describe the nosologic framework of the syndrome and to compare sensibility and specificity for SNAS diagnosis between two different low nickel diets - BraMa-Ni and the usually prescribed list of forbidden foods - along with patient adherence to diet. One hundred forty-five patients with suspected SNAS (by history and benefit from nickel dietary restrictions) were selected and orally challenged with nickel for a definite diagnosis. Specificity and sensibility of the diets were calculated in relation to the results of nickel challenges. The nosologic framework of SNAS was deduced from the clinical pictures of 98 patients with positive nickel challenge and characterized essentially by skin and gastrointestinal symptoms, whereas all other symptoms (dizziness, headache etc.) were never elicited by the oral nickel challenge. The specificity and sensibility of BraMa-Ni in detecting SNAS were significantly higher than the forbidden food list diet, with an excellent patient adherence. Therefore, BraMa-Ni diet can be prescribed for the treatment of the syndrome other than for the diagnosis, the gold standard of which remains the oral nickel challenge.

Distinctive gene expression profiles in Balb/3T3 cells exposed to low dose cobalt nanoparticles, microparticles and ions: potential nanotoxicological relevance.

Size-dependent characteristics of novel engineered nanomaterials might result in unforeseen biological responses and toxicity. To address this issue, we used cDNA microarray analysis (13443 genes) coupled with bioinformatics and functional gene annotation studies to investigate the transcriptional profiles of Balb/3T3 cells exposed to a low dose (1 μM) of cobalt nanoparticles (CoNP), microparticles (CoMP) and ions (Co2+). CoNP, CoMP and Co2+ affected 124, 91 and 80 genes, respectively. Hierarchical clustering revealed two main gene clusters, one up-regulated, mainly after Co2+, the other down-regulated, mainly after CoNP and CoMP. The significant Gene Ontology (GO) terms included oxygen binding and transport and hemoglobin binding for Co2+, while the GOs of CoMP and CoNP were related to nucleus and intracellular components. Pathway analysis highlighted: i) mitochondrial dysfunction for Co2+, ii) signaling, activation of innate immunity, and apoptosis for CoNP, and iii) cell metabolism, G1/S cell cycle checkpoint regulation and signaling for CoMP. Unlike ions, particles affected toxicologically-relevant pathways implicated in carcinogenesis and inflammation.

Immunopathogenesis of sarcoidosis and risk of malignancy: a lost truth?

The hypothesis of a relationship between sarcoidosis and malignancy was firstly formulated in 1972 by Brincker. He documented an association of sarcoid reactions or sarcoidosis with 19 lymphomas and associated malignancies. Based on various epidemiological studies, for more than 20 years sarcoidosis has been considered as a condition at increased risk for cancer, particularly lymphoproliferative disorders. The existence of a sarcoidosis-lymphoma syndrome was therefore proposed, highlighting, as a potential mechanism, the uncontrolled lymphocyte proliferation and mitotic activity. A reduced ability to eliminate an antigen and chronic inflammation have been suggested as triggering events. Leading to a reduced tumor immune surveillance, a diminished myeloid dendritic cells (mDC) function, despite up-regulated co-stimulatory and maturation markers, was also raised as potential mechanism. However, some subsequent studies have questioned the presence of a close association between the two entities and have explained those previously published as the result of selection bias and misclassification. Recently, a Swedish population-based cohort study documented a significant overall excess incidence of cancer among sarcoidosis patients, especially those with multiple hospitalizations or admission in older age, emphasizing again a potential neoplastic risk. Therefore, currently, whether these patients have an increased risk of developing malignant lesions is still debated. Larger and unbiased studies are needed before drawing definite conclusions.

Immune effects of polychlorinated biphenyls, smoking and alcohol.

Polychlorinated biphenyls (PCB) have been shown to exert some immune effects. Here we analysed their effects also on immune parameters not previously studied such as TCR alpha-beta, TCR gamma-delta and regulatory T cells (Treg), taking into account the specific and cumulative interference of smoking and alcohol. The study subjects consisted of 26 male workers in a steel works factory, employed in the electrical maintenance sector, with previous exposure to a mixture of PCB (exposed subjects), and 30 male workers with no occupational exposure to PCB (controls). All subjects were given a questionnaire and peripheral venous blood samples were taken to determine serum PCB (33 congeners), total cholesterol and triglycerides, leukocytes, total lymphocytes and the T lymphocyte subpopulations (TCR alpha-beta, TCRgamma-delta, CD4+ and Treg lymphocytes). PCB, even though at a very low concentration, were significantly higher in exposed subjects than controls, and were significantly correlated with age. Monocytes% and CD4+ were significantly reduced in the exposed subjects as compared to the controls. The serum concentration of PCB positively correlated with TCR alpha-beta, and negatively with TCRgamma-delta. Treg lymphocytes showed a positive dependence on tobacco smoking, while the monocytes percentage and CD4+ showed a negative and positive dependence, respectively, on alcohol intake. Our results seem to show some effects of slight exposure to PCB in particular reducing the relative concentration of TCRgamma-delta. This effect can favour indirectly the increase in Treg induced by smoking, the anti-inflammatory or proinflammatory/fibrogenetic/angiogenetic effect of which, exerted by produced cytokines, particularly TGF-beta, deserves further clarification.

The persistence of allergen exposure favors pulmonary function decline in workers with allergic occupational asthma.

BACKGROUND: In asthmatics, a rapid decline in pulmonary function is observed, likely as a consequence of airways remodeling. Persistence of allergen exposure in patients with occupational asthma (OA) maintains chronic bronchial inflammation, resulting in a more severe lung function decline. Few studies were performed on the effects of allergen exposure cessation. OBJECTIVE: This study aims at evaluating the influence of allergen exposure cessation on respiratory decline in allergic asthmatic workers. METHODS: Two groups of workers with allergic OA were selected. The first group (30 workers) changed job after the diagnosis and was no more exposed to sensitizing allergens, and the second group (28 subjects) did not and, as a consequence of preventive measures in the work place, was exposed to a lower level of allergens. All were treated with conventional therapy, according to GINA protocols. FEV1 changes during a 12-year period were evaluated. RESULTS: Despite pharmacological therapy, the pulmonary function decay slope was steeper in workers continuously exposed to the sensitizing agent (even at reduced level) than in those with a complete cessation of exposure: final FEV1 loss was 512.5 ± 180 ml versus 332.5 ± 108 ml, respectively. The difference became significant after 4 years from the cessation of the exposure. CONCLUSIONS: The study shows that the cessation of the exposure to allergen in the work place appears the most effective measure in limiting pulmonary function decline in asthmatic workers and underlines the importance of allergic risk assessment and control in the management of occupational asthma.

Effects of palladium nanoparticles on the cytokine release from peripheral blood mononuclear cells of non-atopic women.

The object of this study is to determine the cytokine release from PBMCs exposed to Pd model nanoparticles emitted from catalytic converters. PBMCs of 8 healthy non-atopic women were incubated in the presence of Pd nanoparticles (5-10 nm) or salt (potassium hexa-chloropalladate) 10-5 and 10-6 M. Release of cytokines in supernatant of PBMCs was then determined. In cultures without LPS, IL-10 and IL-17 release from PBMCs was inhibited by Pd salt, while Pd nanoparticles inhibited TNF-alpha and IL-17 release. In LPS-stimulated cultures, release of IFN-gamma, TNF-alpha, IL-10 and IL-17 was inhibited by Pd salt, whereas IFN-gamma release was enhanced and TNF-alpha and IL-17 release was inhibited by Pd nanoparticles. In conclusion, Pd salt inhibits cytokine release, whereas Pd nanoparticles exert modulatory effects enhancing the release of IFN-gamma, a Th1 cytokine typical of delayed allergic reactions. This result is interesting considering the increase of allergic contact dermatitis to Pd in people exposed to Pd nanoparticles in urban environments.

Oral hyposensitization to nickel induces clinical improvement and a decrease in TH1 and TH2 cytokines in patients with systemic nickel allergy syndrome.

Some patients with nickel (Ni) allergic contact dermatitis suffer from systemic (intestinal or cutaneous) symptoms after ingestion of Ni-rich foods and experience symptoms reduction with low-Ni diet, a condition termed Systemic Ni Allergy Syndrome (SNAS). We aimed at evaluating whether oral administration of low nickel doses improved clinical conditions and modulated immunological aspects of SNAS, without significant side effects. Thirty-six SNAS patients were enrolled. Treatment started after 1-month of low-Ni diet and consisted in an incremental oral NiOH dose phase (0.3ng to 1.5 microg/week) followed by a 12-months maintenance phase (1.5 microg/week). Randomly, twenty-four patients added Ni therapy to low-Ni diet and 12 remained with diet alone. All patients were allowed rescue medications (antihistamines and topical steroids). After 4 months, Ni-rich foods were gradually reintroduced. In vitro allergen-driven IL13, IL5 and IFN-gamma release by peripheral blood mononuclear cells was evaluated before and after treatment. Twenty-three patients receiving NiOH and the 12 control patients completed the study. Evaluation of SNAS clinical severity (by VAS and drug consumption) showed a significant difference in favor of NiOH-treated patients compared to controls. Twenty of 23 patients in the NiOH group and none in the control group tolerated Ni-rich food reintroduction. Release of all studied cytokines in culture supernatants was significantly lower after NiOH treatment. In conclusion NiOH is effective in reducing symptoms and drug consumption in SNAS and is able to modulate inflammatory parameters.

Bax gene silencing: a potential intervention in aluminum-induced neural cell death.

There is a vast amount of evidence indicating that Bax plays a major role in the development, maintenance, and survival of neurons and neuron-supporting cells such as glial cells. The high potency of Bax small interfering RNA (siRNA), as shown by many experimental studies, makes it a rational candidate as a co-therapeutic agent in apoptotic cell death. To investigate whether Bax RNA interference (RNAi) may serve as a potential intervention in neural cell death induced by aluminum, we herein established aluminum (Al)-treated gliatoma (C6) cells as a model for evaluating neurotoxic injury on normal glia. Using the cell model, we undertook a different approach by inducing glial cell death with Al and then using Bax gene RNAi to suppress glial cell death. Combining cell viability assays and expression analyses by quantitative real-time PCR (qRT-PCR) and immunocytochemistry, we selected and validated the optimal siRNA from 3 candidate siRNAs for the Bax gene. Sequenced reduction of neural cell death was determined with flow cytometry. Our data identified siRNA1 as the most effective siRNA. The optimal concentration of the transfection agent was 20 nM and the optimal incubation period was 72 h. The transfection and knockdown efficiencies were 95 percent and 62 percent, respectively, which closely correlated with Bax protein expression and also the cell apoptosis intervention. Taken together, Bax is essential for apoptosis induced by aluminum. Inactivation of the Bax gene could be an effective strategy for delaying the onset of apoptosis induced by Al. Our results reveal promising therapeutic potential for Bax gene silencing in Al-induced neurodegeneration.

Prevention of surgery in children with adenoidal hypertrophy treated with intranasal flunisolide: a 12-month follow-up.

Adenoidal hypertrophy (AH) represents one of the most frequent indications for surgery in children. Recently, treatment with intranasal corticosteroids has been suggested to decrease the size of AH. The aim of the study is to evaluate the long-term effect of intranasal flunisolide on AH during a 12-month follow-up. One hundred seventy-eight children with a grade III or IV AH at baseline endoscopic examination were enrolled in this randomised and controlled study. Children were treated with intranasal flunisolide or isotonic saline solution for 8 weeks. Subsequent assessment, including history and fiberoptic endoscopy, was made at 8 weeks, and 6 and 12 months after treatment suspension. Flunisolide treatment was initially associated with significant (p<0.01) reduction of the degree of AH. However, during follow-up all but one of the non-allergic children relapsed, whereas most allergic children maintained AH size reduction (p<0.05). No clinically important adverse events were reported. In conclusion, this preliminary study demonstrates that an 8-week treatment with intranasal flunisolide is significantly associated with reduction of AH, however, the adenoidectomy avoidance was warranted only for allergic children.

Inhaled thiamphenicol and acetylcysteine in children with acute bacterial rhinopharyngitis.

Antibiotic abuse for treating rhinopharyngitis induces the occurrence of resistant bacteria. As topical drugs might reduce this phenomenon, the aims of our study are to evaluate inhaled thiamphenicol associated with acetylcysteine in children with acute bacterial rhinopharyngitis and to compare it with the use of saline solution. The trial was conducted as randomized, parallel group, and single blind. Children, aged 3-6 years, with acute bacterial rhinopharyngitis were treated with aerosolized thiamphenicol associated with acetylcysteine (250 mg: 1/2 vial in the morning and 1/2 vial in the evening) (Group A) or saline solution twice daily (Group B), both of them for 5 days. Both treatments were administered using a new device: Rinowash. The following parameters were assessed: nasal obstruction, mucopurulent rhinorrhea, post-nasal drip, cough, sore throat, fever, and cultures. Of 104 patients screened, 90 children, median age 3.7 years (44 females and 46 males), completed the study: 60 in Group A and 30 in Group B. Actively-treated children achieved a significant improvement of all parameters, but fewer than the control group. In conclusion, inhaled thiamphenicol associated with acetylcysteine may represent a valid treatment for acute bacterial rhinopharyngitis in children, as it is effective, safe, economic, and simple to use.

Non-allergic rhinitis with eosinophils and mast cells constitutes a new severe nasal disorder.

Three main types of inflammatory Non-Allergic Rhinitis (NAR) have been defined: NAR infiltrated by eosinophils (NARES), by mast cells (NARMA), and by neutrophils (NARNE). A new particular type has been characterized with current infiltration by eosinophils and mast cells (NARESMA). The aim of this study is to evaluate the clinical and functional characteristics in patients with NARES, NARMA, NARNE, and NARESMA and to define the latter. One hundred and seventy-six NAR patients were prospectively and consecutively evaluated: 52 patients with NARES, 38 with NARMA, 36 with NARNE, and 50 with NARESMA. Clinical features, Quality of Life (QoL), and rhinomanometry were evaluated in all of them. QoL was significantly different in the 4 groups. NARESMA patients had the worst QoL. Nasal function and QoL in NARESMA patients were significantly correlated. Significant associations were shown with both nasal polyps and asthma in NARESMA patients. This study provides the first evidence that NARESMA constitutes a new type of NAR and is a particularly severe disorder.

How do rat cortical cells cultured with aluminum die: necrosis or apoptosis?

Aluminum (Al) exposure has been implicated as the cause of neural cells loss in several neurodegenerative diseases. Therefore, defining the mechanism of neural cell death in Al toxicity and degenerative diseases might lead to the development of therapeutic agents which promote neural cell survival. Furthermore, knowledge of cell death pathways might facilitate the discovery of treatments for neurodegeneration. However, the death mode of neural cells triggered by Al has not been firmly established. The present study focuses on understanding the pathway of cells death in cultured cortical cells treated with Al. Primary neurons cultured alone, astrocytes cultured alone, and neuron/astrocyte co-cultures obtained from newborn rats were incubated with Al at the concentrations of 0, 0.5, 1.0, or 2.0 mM for 72 h. Morphological changes were observed with an inverted phase microscope, a fluorescent microscope, and an electron microscope. Simultaneously, the rate of apoptosis was quantified with flow cytometry. Morphological characteristics of apoptosis such as cell shrinkage, aggregation and fragmentation of chromatin, membrane buds, and formation of membrane-bound apoptotic bodies were observed in Al-treated neurons, while none of these characteristics were found in Al-treated astrocytes. Quantitative results of apoptotic rates detected with flow cytometry indicated a typical apoptosis progression in neurons at various dosages. A concentration-dependent relationship between Al concentration and apoptotic rates confirmed that apoptosis is the prominent cause of cell death in primary cultured neurons, even at a concentration lower than 2 mM. Both necrosis and apoptosis are evident in neuron/astrocyte co-cultures, but the intensity of apoptosis is much less compared with that of neurons, suggesting that astrocytes may be especially important for neuronal survival in the presence of Al.

Characteristics of patients with allergic polysensitization: the POLISMAIL study.

BACKGROUND: The natural history of respiratory allergy is commonly characterized by a worsening of symptom severity, frequent comorbidity of rhinitis and asthma, and polysensitization to aeroallergens. The polysensitization phenomenon starts since childhood and is rare to find monosensitized adult patients. However, there are few studies investigating the characteristics of polysensitized patients. METHODS: This study was performed on a large cohort of patients with allergic rhinitis (assessed by ARIA criteria) and/or mild to moderate asthma (assessed by GINA). The kind and the number of sensitizations, their patterns, and the relation with quality of life (QoL) measured by the Juniper's RQLQ guestionnaire, were evaluated. RESULTS: Globally 418 patients (50.2% males, 49.8% females, mean age 26.4 years, range 3.5-65 years, 64 smokers, 371 non-smokers) were enrolled: 220 had allergic rhinitis alone, and 198 allergic rhinitis and asthma. The mean number ofsensitizations was 2.6. Three hundred-five patients (73%) had persistent rhinitis (PER), 220 of them with moderate-severe form. There was no significant derence in rate of rhinitis and asthma in monosensitized or polysensitized patients. Most patients were sensitized to pollens, whereas only 24.2% of them were sensitized to perennial allergens. Polysensitization was significantly associated with some issues of QoL, confirming previous findings, but not with number ofsensitizations. CONCLUSIONS: This study provides data confirming for poly-sensitized patients the relevance of ARIA classification of AR. PER is the most common form of AR in this cohort, symptoms are frequently moderate-severe, and asthma is present in about the half of patients with AR.

Combined effects of electromagnetic fields on immune and nervous responses.

In technologically developed countries, there is concern about hazards from electromagnetic fields (EMFs). Several studies have reported that immune and neuroendocrine systems exert an integrated response to EMF exposure. The aim of this review is to summarize the results of studies on the effect of low and high frequency EMF on immune and neuroendocrine systems on which our research group has been working for several years.

The relationship between Bcl-gene expression and learning and memory impairment in chronic aluminum-exposed rats.

Aluminum (Al), a known neurotoxin, has been implicated in Alzheimer's Disease (AD), Amyotrophic Lateral Sclerosis (ALS), Parkinsonism Dementia Complex, etc., and it causes extensive damage to the nervous system, including the impairment of learning and memory. However, to date, the mechanism of Al neurotoxicity has not been fully elucidated. Neuronal apoptosis has become a focus of interest, as it has been reported to play a key role in the impairment of learning and memory processes (Thompson, Science 267:1456, 1995). The Bcl-2 gene acts as an important effector for inhibiting apoptosis. In the present study we observe neuronal apoptosis in association with learning and memory impairment, as well as regional brain alterations in Bcl-2 expression in rats chronically exposed to Al. The chronic Al-intoxicated model was established by i.p. injection of AlCl3 in adult Sprague Dawley rats for 3 successive days, with one-day intervals, for 60 days. After exposure, the step-down test was performed to examine the behavioral reaction of the rats. Neuronal apoptosis and Bcl-2 protein expression in different regions of rat brain were then assessed by an immunohistochemical method. In the step-down test, the latency of Al-exposed rats was significantly lower than that of controls. Also, the number of performance errors in 5 minutes of exposure was significantly higher than that of controls. Neuronal apoptosis was extensive in the brain of Al-exposed groups, and the expressions of Bcl-2 protein in frontal cortex, cerebellum and hippocampus of Al-exposed rats was stronger. In conclusion, chronic Al-exposure in rats is associated with neuronal apoptosis in brain, and impaired learning and memory. Augmented Bcl-2 protein expression may be a stimulated compensatory mechanism.

Follow up study on the immune response to low frequency electromagnetic fields in men and women working in a museum.

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.

The immune response of women with prolonged exposure to electromagnetic fields produced by radiotelevision broadcasting stations.

Twelve women, five of them housewives, exposed in their residences to electromagnetic fields (EMFs)emitted by radio-television broadcasting stations for a mean period of 13 years, were investigated. The EMFs in the balconies of the homes were (mean + S.D.) 4.3 + 1.4 V/m in the year 2000 and 3.7 + 1.3 V/m in 2005, while the exposure in the nearby area was <2.0 V/m. The EMF exposed women showed in 2000 reduced blood NK lymphocytes as well as PHA stimulated PBMC proliferation and IL-2 and IFN-gamma release. In the year 2005, the EMF exposed women and 48 control women with similar ages(mean 43 years), smoking habits, atopy and social level were investigated. State (temporary) and trait(tendency of the personality) anxiety were determined by STAI I and II, respectively. Blood cytotoxic activity and lymphocyte subsets were also determined. The ratio STAI I/STAI II of the EMF exposed group was lower than that of the control group. The blood cytotoxic activity of the exposed women was lower (p<0.01), percent of B CD45+-CD19+ lymphocytes higher and percent of CD45+-CD3+-CD8+ cells lower (p<0.05). Moreover, cytotoxic activity/CD45+-CD16+-56+ NK lymphocytes of the controls was negatively correlated with STAI I and STAI II (p<0.001). In conclusion, this study demonstrates reduced blood cytotoxic activity and increased trait anxiety in relation to state anxiety in EMF exposed women. An effect of EMFs on immune functions, in part mediated by nervous mechanisms, may be hypothesized. However, the influence of lifestyle may not be excluded.