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We present some preliminary results on the mapping of coseismically-induced ground ruptures following the Aug. 24, 2016, Central Italy earthquake (Mw 6.0). The seismogenic source, as highlighted by InSAR and seismological data, ruptured across two adjacent structures: the Vettore and Laga faults. We collected field data on ground breaks along the whole deformed area and two different scenarios of on-fault coseismic displacement arise from these observations. To the north, along the Vettore fault, surface faulting can be mapped quite continuously along a well-defined fault strand while such features are almost absent to the south, along the Laga fault, where flysch-like marly units are present. A major lithological control, affects the surface expression of faulting, resulting in a complex deformation pattern.

The article offers information on round table titled "COVID-19: commitment of French ministry of the armed forces to vaccinate its community and the French population" presented at 1st European Union (EU) Congress on Military Health Services. It mentions Comirnaty mRNA vaccine solution was selected because it provided a shorter completion schedule. It also mentions military medical supply and public-health care actors were strong partners to deliver the vaccine and report the campaign.

Background: Eyelid ptosis is an underestimated pathology deeply affecting patients' quality of life. Internet has increasingly become the major source of information regarding health care, and patients often browse on websites to acquire an initial knowledge on the subject. However, there is lack of data concerning the quality of available information focusing on the eyelid ptosis and its treatment. We systematically evaluated online information quality on eyelid ptosis by using the "Ensuring Quality Information for Patients" (EQIP) scale., Materials and Methods: Google, Yahoo and Bing have been searched for the keywords "Eyelid ptosis," "Eyelid ptosis surgery" and "Blepharoptosis." The first 50 hits were included, evaluating the quality of information with the expanded EQIP tool. Websites in English and intended for general non-medical public use were included. Irrelevant documents, videos, pictures, blogs and articles with no access were excluded., Results: Out of 138 eligible websites, 79 (57,7%) addressed more than 20 EQIP items, with an overall median score of 20,2. Only 2% discussed procedure complication rates. The majority fail to disclose severe complications and quantifying risks, fewer than 18% clarified the potential need for additional treatments. Surgical procedure details were lacking, and there was insufficient information about pre-/postoperative precautions for patients. Currently, online quality information has not improved since COVID-19 pandemic., Conclusions: This study highlights the urgent requirement for improved patient-oriented websites adhering to international standards for plastic and oculoplastic surgery. Healthcare providers should effectively guide their patients in finding trustworthy and reliable eyelid ptosis correction information., Level of Evidence V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Wireless sensor network (WSN) deployment is an intensive field of research. In this paper, we propose a novel approach based on machine learning (ML) and metaheuristics (MH) for supporting decision-makers during the deployment process. We suggest optimizing node positions by introducing a new hybridized version of the "Hitchcock bird-inspired algorithm" (HBIA) metaheuristic algorithm that we named "Intensified-Hitchcock bird-inspired algorithm" (I-HBIA). During the optimization process, our fitness function focuses on received signal maximization between nodes and antennas. Signal estimations are provided by the machine learning "K Nearest Neighbors" (KNN) algorithm working with real measured data. To highlight our contribution, we compare the performances of the canonical HBIA algorithm and our I-HBIA algorithm on classical optimization benchmarks. We then evaluate the accuracy of signal predictions by the KNN algorithm on different maps. Finally, we couple KNN and I-HBIA to provide efficient deployment propositions according to actual measured signal on areas of interest.

Surface faulting earthquakes are known to cluster in time from historical and palaeoseismic studies, but the mechanism(s) responsible for clustering, such as fault interaction, strain-storage, and evolving dynamic topography, are poorly quantified, and hence not well understood. We present a quantified replication of observed earthquake clustering in central Italy. Six active normal faults are studied using 36 Cl cosmogenic dating, revealing out-of-phase periods of high or low surface slip-rate on neighboring structures that we interpret as earthquake clusters and anticlusters. Our calculations link stress transfer caused by slip averaged over clusters and anti-clusters on coupled fault/shear-zone structures to viscous flow laws. We show that (1) differential stress fluctuates during fault/shear-zone interactions, and (2) these fluctuations are of sufficient magnitude to produce changes in strain-rate on viscous shear zones that explain slip-rate changes on their overlying brittle faults. These results suggest that fault/shear-zone interactions are a plausible explanation for clustering, opening the path towards process-led seismic hazard assessments., (© 2022. The Author(s).)

We provide here a first-hand description of the coseismic surface effects caused by the Mw 6.4 Petrinja earthquake that hit central Croatia on 29 December 2020. This was one of the strongest seismic events that occurred in Croatia in the last two centuries. Field surveys in the epicentral area allowed us to observe and map primary coseismic effects, including geometry and kinematics of surface faulting, as well as secondary effects, such as liquefaction, sinkholes and landslides. The resulting dataset consists of homogeneous georeferenced records identifying 222 observation points, each of which contains a minimum of 5 to a maximum of 14 numeric and string fields of relevant information. The earthquake caused surface faulting defining a typical 'conjugate' fault pattern characterized by Y and X shears, tension cracks (T fractures), and compression structures (P shears) within a ca. 10 km wide (across strike), NW-SE striking right-lateral strike-slip shear zone (i.e., the Petrinja Fault Zone, PFZ). We believe that the results of the field survey provide fundamental information to improve the interpretation of seismological, GPS and InSAR data of this earthquake. Moreover, the data related to the surface faulting may impact future studies focused on earthquake processes in active strike-slip settings, integrating the estimates of slip amount and distribution in assessing the hazard associated with capable transcurrent faults.

Objective: The objective of this study was to assess the links between temperament and sleep in a group of preschoolers with ADHD. Method: Twenty-five ADHD ( M = 5.37 years, SD = 1.09) and 22 typically developing (TD; M = 5.10, SD = 1.18) preschoolers participated in the study. Sleep was assessed with the Sleep Disturbance Scale and wrist actigraphy. The Preschool Temperament and Character Inventory (PsTCI) was used to evaluate the child temperament. Results: ADHD children showed a temperamental profile characterized by higher novelty seeking, lower persistence, self-directness, and cooperativeness and marginally lower harm avoidance (HA) compared with controls. HA was associated negatively to wakefulness after sleep onset and sleep fragmentation and positively with sleep efficiency and sleep time. Reward dependence was negatively associated with wake episode length. Conclusion: Sleep and temperament are correlated in preschoolers with ADHD and temperament might represent an intermediate endophenotype underlying the relation between ADHD and sleep disorders.

Objective: To assess the features of sleep in preschoolers with ADHD by means of questionnaire and actigraphy. Method: Twenty-five ADHD and 21 age-matched typically developing (TD) preschool children underwent the Child Behavior Checklist (CBCL) for ages 1½ to 5 and Pre-School-Age Psychiatric Assessment interview. Sleep was assessed by means of a modified Sleep Disturbance Scale for Children and wrist actigraphy for at least 5 days. Results: Children with ADHD, compared with TD, showed higher scores in CBCL Withdrawal (58.83 vs. 51.15, p < .0001), Attention Problems (69.88 vs. 51.54, p < .0001), and Aggressive Behavior (59.46 vs. 51.08, p < .0001) dimensions; they also showed increased actigraphic nocturnal activity (activity index 31.57 vs. 25.74, p < .05); and night-to-night variability for sleep minutes (56.44 vs. 32.79, p < .01), mean wake episodes (1.34 vs. 0.98, p < .05), mean activity (2.64 vs. 1.71, p < .05), and activity index (5.15 vs. 3.77, p < .05). Conclusion: This pilot study in preschoolers with ADHD showed increased motor activity during sleep and night-to-night variability for sleep duration and motor activity.

Objective: This study aims to develop an age-adjusted Child Behavior Checklist- (CBCL) and Teacher Report Form (TRF)-based method for the detection of deficient emotional self-regulation (DESR) in preschoolers with ADHD and to assess its incidence, comorbidities, and consequences on interpersonal functioning., Method: Eighty-six ADHD preschoolers and 104 controls were assessed using CBCL, TRF/1½ to 5, Psychiatric Interview With Preschool Age Psychiatric Assessment, Leiter-R, and ADHD rating scales., Results: Greatest sensitivity and specificity were obtained applying slightly lower threshold scores compared with school-age children (CBCL: Anxiety/Depression [A/D] ≥ 59, Attention Problems [AP] ≥ 60, Aggression Behaviors [AB] ≥ 58; TRF: A/D ≥ 59, AP ≥ 60, AB ≥ 60). DESR was detected in 33/86 (38.4%) and in 16/54 (29.6%) ADHD preschoolers versus 2/104 (1.9%) controls using CBCL and TRF, respectively. DESR is associated with significantly greater comorbidity and impairment in interpersonal functioning., Conclusion: Among ADHD preschoolers, DESR (a) requires lower CBCL and TRF threshold scores for detection, compared with school-age children, (b) displays similar incidence rates, and (c) is associated with enhanced psychiatric comorbidity and interpersonal difficulties.

Among lifestyle factors, nutrition is one of the most important determinants of health, and represents a pivotal element of cancer risk. Nonetheless, epidemiological evidences of the relationship between several cancers and specific foods and nutrients is still inadequate, and solid conclusions are missing. Indeed, caloric restriction without malnutrition is associated to cancer prevention. Food may be also the primary route of exposure to contaminants such as metals, persistent organic pollutants, and pesticides. Exposuredisease associations and the interplay with genetic susceptibility requires further studies on genetic variation, environment, lifestyle, and chronic disease in order to eliminate and reduce associated health risks, thus contributing to improve health outcomes for the population. A primary nutritional approach for Active and Healthy Ageing (AHA) has been developed by the Nutrition group of the European Innovation Partnership (EIP) on AHA. The working group on lifestyles of the Italian Ministry of Health has developed a comprehensive approach to adequate nutrition using a consensus methodology to collect and integrate the available evidences from the literature and from the Italian experiences at the regional level, to raise the interest of other experts and relevant stakeholders to outline and scale-up joint strategies for a primary nutritional approach to cancer prevention.

Study Objectives: To analyze sleep in children with Asperger syndrome (AS) by means of standard sleep questionnaires, to evaluate sleep architecture and NREM sleep alterations by means of cyclic alternating pattern (CAP) and to correlate objective sleep parameters with cognitive behavioral measures., Design: Cross-sectional study involving validated sleep questionnaires, neuropsychological scales, and PSG recording., Setting: Sleep medicine center., Participants: Eight children with AS, 10 children with autism, and 12 healthy control children., Interventions: N/A., Measurements and Results: Children with AS had a higher prevalence of problems of initiating sleep and daytime sleepiness. Sleep architecture parameters showed minor differences between the 3 groups. CAP parameters showed an increased percentage of A1 and a decreased percentage of A2 subtypes in subjects with AS vs. controls. All A subtype indexes (number per hour of NREM sleep) were decreased, mostly in sleep stage 2 but not in SWS. With respect to children with autism, subjects with AS showed increased CAP rate in SWS and A1 percentage. In subjects with AS, verbal IQ had a significant positive correlation with total CAP rate and CAP rate in SWS and with global and SWS A1 index. The percentage of A2 negatively correlated with full scale IQ, verbal and performance IQ. CBCL total score correlated positively with CAP rate and A1 index while externalizing score correlated negatively with A3%., Conclusions: This study shows peculiar CAP modifications in children with AS and represents an attempt to correlate the quantification of sleep EEG oscillations with the degree of mental ability/disability.

Study Objectives: To evaluate the characteristics of the cyclic alternating pattern (CAP) in the sleep of preschool-aged children in order to obtain normative parameters in this age range., Design: Prospective study., Settings: University sleep laboratory., Participants: Ten normal healthy subjects (6 girls and 4 boys, mean age 4.6 years; range 3-6 years) underwent polysomnography recordings for 2 consecutive nights in a standard laboratory setting. Sleep data were stored on a computer using a polysomnography digital system (Embla N7000, Medcare, Iceland). Sleep structure was visually scored according to the Rechtschaffen and Kales criteria. The cyclic alternating pattern was visually scored following the criteria by Terzano et al. These criteria were modified for the purposes of this study because it was noticed that, at the age of the group under analysis, most electroencephalogram arousals, often accompanied by electromyogram activation, are expressed at the level of the electroencephalogram by theta frequencies and not alpha or higher frequencies., Measurements and Results: The CAP rate in preschool-aged children (25.93%) showed a progressive increase with the deepness of sleep, with highest values during non-rapid eye movement (NREM) stage 3 (44.0%) and 4 sleep (46.08%) and lowest values in NREM stage 2 (17.26%). The CAP time showed its longest duration during stage 2 sleep, followed by stage 4, stage 3, and NREM stage 1. The CAP cycle duration showed no differences across NREM stages. The cyclic alternating pattern phase A was longer and phase B was shorter during stage 1 than during stages 2, 3, and 4. A1 phases were the most numerous (63.2%), followed by A2 (21.5%) and by A3 (15.3%). The distribution of A-phase subtypes across NREM sleep stages (A index) showed significant differences for the A1 subtypes that occurred more frequently during stage 3 and 4 sleep than during stages 1 and 2. The A2 index showed no significant differences across NREM sleep stages, while the A3 index was significantly higher during stage 1 sleep than during stages 2, 3, and 4. The analysis of the A1 interval distribution showed a log-normal-like distribution with a peak around 25 seconds for the A1 phases and no clear peak for A2-A3 phases., Conclusions: The analysis of CAP in preschool-aged children is characterized by an increase of CAP rate during slow-wave sleep and a high percentage of A1 phases and A2 phases. However, the lower percentage of A1 paralleled by an increase of A2 could represent a signal of higher sleep instability in this age group as compared with prepubertal school-aged children.

Objectives: To evaluate cyclic alternating pattern (CAP) in sleep of school-age children in order to obtain a standardized database for CAP parameters in this age range., Methods: CAP parameters were quantified in 10 normal healthy subjects (6 males and 4 females, mean age 8.3 years; range 6-10 years). All subjects underwent polysomnography recordings for two consecutive nights in a standard laboratory setting. Sleep data were stored on computer using a 16-channel polysomnography digital system. Sleep macrostructure was visually scored according to the criteria by Rechtschaffen and Kales (Brain Information Service/Brain Research Institute, University of California, Los Angeles, 1968); CAP was visually scored following the criteria by Terzano et al. (Sleep Med 2 (2001) 537)., Results: CAP rate showed a progressive increase with the deepness of sleep, with high values during slow wave sleep (SWS). CAP time showed its longest duration during non-REM (NREM) sleep stage 2 (S2), followed by SWS and sleep stage 1 (S1). No differences across NREM sleep stages were found for CAP cycle and phase B mean duration; on the contrary, phase A showed longer duration during SWS than in S1 and S2. Phases A1 were the most numerous (84.45%) followed by A3 (9.14%) and by A2 (6.44%). The distribution of phases A subtypes across NREM stages showed significant differences for the A1 subtypes that occurred more frequently during SWS than in S2 and S1 (and during S2 than in S1). Subtypes A3 were more frequent during S1 than SWS while no differences were found for subtype A2. The analysis of A1 interval distribution showed a log-normal-like distribution with a peak around 25 s for the A1 phases and no clear peak for A2-A3 phases., Conclusions: The analysis of CAP in school-age children is characterized by an increase of CAP rate during SWS and a high percentage of A1 phases. The distribution of interval between consecutive A1 phases showed a peak around 25 s.

To clarify the impairment of the GH/IGF-I axis in obstructive sleep apnea syndrome (OSAS), in 13 adult male patients with OSAS (OSA) as well as 15 weight-matched patients with simple obesity (OB) and 10 normal lean male subjects (NS), we studied: 1) the GH response to GHRH (1 micro g/kg iv) plus arginine (30 g iv); and 2) the IGF-I and IGF binding protein-3 responses to a very low dose recombinant human (rh)GH treatment (5.0 microg/kg sc per day for 4 d). The GH response to arginine plus GHRH in OSA was lower than in OB (P < 0.05), which in turn was lower than in NS (P < 0.001). Basal IGF-I levels in OSA were lower than in OB (P < 0.05), which in turn were lower than in NS (P < 0.03). As opposed to OB and NS, in OSA a very low rhGH dose did not affect IGF-I. Adjusting for age and basal values, rhGH-induced IGF-I rise in OSA was lower than in OB (P < 0.01). IGF binding protein-3, glucose, and insulin levels in the three groups were not modified by rhGH. OSA show a more marked impairment of the maximal secretory capacity of somatotroph cells together with reduced IGF-I sensitivity to rhGH stimulation. These findings suggest that OSAS is connoted by a concomitant impairment of GH secretion and sensitivity.

Methods: To examine the inflammatory process in chronic bronchitis, we evaluated the cell and cytokine profile in bronchoalveolar lavage fluid from 12 chronic bronchitis patients who smoked, six chronic bronchitis patients who did not smoke, 10 subjects control subjects without pulmonary diseases who smoked and eight control subjects who did not smoke., Results: Chronic bronchitis patients who smoked had increased numbers of macrophages, neutrophils, eosinophils, mast cells and activated CD8+ T lymphocytes and predominantly expressed interleukin-8, tumour necrosis factor alpha and interleukin-2 genes and proteins. The number of macrophages and neutrophils and the expression of interleukin 8 were also increased in control subjects who smoked compared with healthy subjects who did not smoke. Chronic bronchitis patients who did not smoke had increased numbers of eosinophils, mast cells and activated CD4+ T lymphocytes and predominantly expressed interleukin-5 and granulocyte-macrophage colony-stimulating factor genes and proteins., Conclusion: Thus, the cellular and molecular characteristics of the inflammatory process in chronic bronchitis patients who smoke and do not smoke are different, suggesting a different pathogenesis of the disease.

RANTES is a cytokine produced by activated T-lymphocytes that has been shown to exert chemotactic activity for memory-type CD4 T-lymphocytes and eosinophils. In this study, RANTES caused directional migration of human mast cells. When compared to other potential chemoattractants of the same cells, RANTES was found to be more potent than fibronectin and the c-kit receptor ligand, on a molar basis. This cytokine may be a common mechanism in allergic reactions which culminate in the selective migration of memory CD4 T-lymphocytes, eosinophils and mast cells at the tissue site. Asthma and allergic rhinitis may represent possible clinical examples.

This study evaluated immunoreactivity for several cytokines in bronchial tissue of asthmatic patients and related this to the clinical and functional characteristics. Patients were allocated into two different groups on the basis of their atopic status (atopic and nonatopic), with two subgroups of symptomatic and asymptomatic subjects in each. Five healthy volunteers were tested as control subjects. After clinical and functional assessment, all of the subjects underwent bronchoscopy. Several biopsy specimens were obtained for immunohistochemical and immunoelectron microscopic evaluation. Symptomatic asthmatic subjects had increased expression of immunoreactive interleukin (IL) 1 beta, IL-2, IL-3, IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor alpha (TNF alpha) when compared to the asymptomatic patients or normal control subjects. The cell sources of IL-1 beta were monocytes and dendritic cells in atopic patients and monocytes alone in nonatopic asthmatic subjects. The CD4+ T lymphocytes from atopic asthmatic subjects predominantly expressed IL-3, IL-4, IL-5, and GM-CSF immunoreactivity, whereas CD4+ T cells from nonatopic patients predominantly expressed IL-2, IL-3, and IL-5, and GM-CSF immunoreactivity. Mast cells showed immunoreactivity for TNF alpha, IL-3, IL-5, and GM-CSF. Immunostaining for TNF alpha and GM-CSF was also detected in bronchial epithelial cells and monocytes. Tissue eosinophilia and the level of airway hyperresponsiveness more closely correlated with IL-5 immunoreactivity in atopic asthmatic subjects and with IL-2 and GM-CSF immunoreactivity in nonatopic patients.

Twenty-two asthmatic patients with a range of airway hyperresponsiveness to methacholine underwent a bronchial challenge with ultrasonically nebulized distilled water (UNDW). The presence of positive responses to this stimulus was related to the extent of airway inflammation, as assessed by histochemical and immunohistochemical evaluation of bronchial biopsy specimens. Twelve patients had airflow obstruction during distilled water inhalation and they showed more severe disease than subjects with no response, as demonstrated by the higher degree of nonspecific bronchial hyperresponsiveness (p < 0.01), higher variability of peak expiratory flow rates (p < 0.01), symptom scores (p < 0.01), and daily use of bronchodilators (p < 0.01). Those patients also had increased numbers of mast cells and eosinophils (p < 0.01) and increased percentage of bronchial epithelial cells expressing endothelin 1 immunoreactivity (p < 0.01). Thus, positive responses to inhaled UNDW reflect the bronchial hyperresponsiveness consistent with moderate to severe asthma and may be due to the release of mediators with bronchoconstrictive properties from inflammatory cells or activated resident cells or both.

Background: T lymphocytes may orchestrate the inflammatory response in atopic asthma, but the mechanisms that promote T-cell accumulation in asthmatic airways are still unclear. In this study, we tested the hypothesis that bronchial epithelial cells of patients with atopic asthma release chemoattractant factors for T lymphocytes., Methods: Sixteen patients with atopic asthma and eight healthy control subjects were selected for this study. Bronchial epithelial cells were isolated from biopsy specimens obtained by means of bronchoscopy and cultured for 48 hours in serum- and hormone-free medium, with or without 10(-6) mol/L histamine., Results: Only the supernatants of cells from donors with asthma showed chemotactic activity for T lymphocytes, and this was significantly increased (p < 0.025) by exposure to histamine. Chemotactic activity was in part mediated by interleukin-8 (IL-8), because an antibody against human IL-8 significantly reduced it (p < 0.05) and the cell supernatants contained appreciable amounts of immunoreactive IL-8 (0.89 +/- 0.39 ng/ml). Both the residual chemotactic activity of unstimulated epithelial cells and the increased activity caused by histamine were mediated by a single protease-sensitive substance with an apparent molecular weight of 56,000 d and an estimated isoelectric point of 8.8 to 9.1. The partially purified chemoattractant specifically enhanced the migration of CD4+ T lymphocytes, and its activity was inhibited by the univalent Fab fragment of a monoclonal antibody against CD4., Conclusion: These results extend our previous observations, indicating an important effector role of bronchial epithelium in asthma.

This study examines the distribution of intraepithelial dendritic cells in eight atopic patients with symptomatic asthma and their ability to induce activation of autologous T lymphocytes in vitro. All subjects were sensitized to Dermatophagoides pteronyssinus. The incubation of asthmatic epithelial cells and dendritic cells with autologous resting CD4-positive T cells and purified extracts of D pteronyssinus induced T cell activation and release of high levels of interleukin-4 (IL-4) and interleukin-5 (IL-5). The antigen-presenting activity of dendritic cells was potentiated by epithelial cell-derived granulocyte-macrophage colony-stimulating factor (GM-CSF), since an antibody against GM-CSF reduced it. Circulating monocytes of the two groups of donors were equally effective in promoting selective activation of IL-4- and IL-5-producing T cells. Thus, an interaction between dendritic cells and allergens may favor local activation of CD4-positive T cells with Th2-like function in atopic asthmatic subjects, thereby promoting the expression of the disease.

We have previously demonstrated that human bronchial smooth muscle cells possess specific binding sites for the potent bronchoconstrictive peptide endothelin 1 and that primary cultures of human bronchial epithelial cells constitutively produce an endothelin-like material that binds to smooth muscle cell receptors with a kinetic ability analogous to that shown by the authentic peptide. To evaluate the potential role of airway epithelium-derived endothelin in the pathogenesis of asthma, we have examined here the expression of endothelin in the bronchial epithelial cells of 6 patients with symptomatic asthma and reversible airflow obstruction. The epithelial cells of 5 normal volunteers and 5 patients with chronic bronchitis and airflow obstruction unaffected by bronchodilators were tested as controls. The bronchial epithelial cells of all the asthmatic patients expressed preproendothelin 1 mRNA, as assessed by in situ hybridization, and released high amounts of mature and biologically active endothelin during a 48-h period of incubation (radioimmunoassay). By contrast, the epithelial cells from normal donors did not contain preproendothelin 1 transcripts, and the endothelin-like material in their supernatants was invariably below the detection limit of the assay. Only a few cells from 2 patients with chronic bronchitis expressed preproendothelin mRNA and endothelin immunoreactivity. When hydrocortisone (10(-6)M) was added to the culture medium of asthmatic bronchial epithelial cells for 48 h, the release of immunoreactive endothelin significantly decreased (p < 0.025), but the numbers of cells expressing preproendothelin 1 mRNA did not change to the same extent.

Cellular constituents of the bronchial mucosa may participate in the recruitment of polymorphonuclear leukocytes to the inflamed airways through the generation of the neutrophil chemotactic peptide, interleukin-8 (IL-8). One important aspect of this interaction could be represented by the ability of pulmonary monokines, particularly IL-1, to induce gene expression of IL-8 in bronchial epithelial cells. In this study, we have evaluated the constitutive and IL-1-induced production of IL-8 by cultured human bronchial epithelial cells and examined the ability of the anti-inflammatory drug, nedocromil sodium, to inhibit the cytokine synthesis and release. Northern blot analysis demonstrated that IL-1 beta-treated human bronchial epithelial cells expressed appreciable levels of IL-8 mRNA during a period of 8 hours. This finding was associated with an increased release of immunoreactive IL-8 to the culture media, as assessed by specific ELISA. The bronchial epithelial cell-derived IL-8 demonstrated specific biologic activity, since the supernatants of stimulated bronchial epithelial cells possessed neutrophil chemotactic activity that could be inhibited by an antibody against human IL-8. Nedocromil sodium reduced the IL-1-induced release of IL-8 in a dose-dependent manner, but concentrations of the compounds, up to 10(-5) mol/L, did not affect the constitutive production of this cytokine.

We have previously demonstrated that cultured human bronchial epithelial cells produce cytokines with potent proinflammatory properties on exposure to several stimuli in vitro, and we have hypothesized that these epithelial cell-derived factors may contribute to the pathogenesis of some inflammatory diseases of the bronchial mucosa, particularly asthma, by promoting the infiltration of granulocytes and T cells and their local activation. We provide, in this study, direct evidence of an increased expression of granulocyte-macrophage-colony-stimulating factor, interleukin-6, and interleukin-8 genes and proteins in bronchial epithelium from patients with symptomatic asthma. The up regulation of the production of these cytokines in bronchial epithelial cells of patients with asthma could be abolished in vitro by corticosteroids (hydrocortisone, 10(-7) mol/L), but the up regulation also spontaneously disappeared during a period of 6 days after the removal of the cells from the diseased tissue.