RESUMEN
In an earlier study, we showed that a recombinant adenovirus vector with deletions in the E1 and E3 regions of the viral genome (AV1LacZ4) induces expression of interleukin (IL)-8 in A549 cells (a human respiratory cell line). IL-8 can be induced through several pathways, including activation by IL-1. We tested the hypothesis that the induction of IL-8 by the AV1LacZ4 adenovirus is accomplished by means of the IL-1/IL-8 activation pathway, which could be blocked by IL-1 receptor antagonist (IRAP). Viral infections of A549 cells were performed at a multiplicity of infection (MOI) of 50 in the presence and absence of IRAP (50 ng/ml). A549 cells were also stimulated with tumor necrosis factor (TNF)-alpha (100 ng/ml), a known stimulant of IL-8, in the presence and absence of IRAP. IL-8 expression was evaluated by Northern blot analysis and enzyme-linked immunosorbent assay. Levels of IL-8 protein and messenger RNA (mRNA) were greater in the infected cells than in the uninfected ones at 24, 48, and 96 h (P < 0.01). Virus-infected cells treated with IRAP expressed 75% less IL-8 mRNA and protein (P < 0.01) than did untreated cells, whereas IRAP pretreatment of TNF-alpha-stimulated cells did not affect IL-8 production. IL-1 production by the virus-infected cells was detectable by concentration of the supernatants and reverse transcription-polymerase chain reaction. We conclude that IL-8 is produced by virus vector-infected cells, partly through IL-1 activation that can be downregulated by IRAP.
Asunto(s)
Adenoviridae/genética , Bronquios/efectos de los fármacos , Interleucina-8/metabolismo , Receptores de Interleucina-1/antagonistas & inhibidores , Sialoglicoproteínas/farmacología , Virus Defectuosos/genética , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo , Células Epiteliales/efectos de los fármacos , Vectores Genéticos , Humanos , Proteína Antagonista del Receptor de Interleucina 1 , Interleucina-1/farmacología , Interleucina-1/fisiología , Proteínas Recombinantes/metabolismo , Recombinación Genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Tiempo , Células Tumorales CultivadasRESUMEN
BACKGROUND: Medical screening is used routinely to qualify and classify candidates for pilot training. The respiratory system assumes even greater importance owing to the increased stress of flying high-performance aircraft in a hostile environment characterized by high altitude, varying acceleration ("G" forces), and the possibility of rapid decompression. Any respiratory dysfunction may threaten the pilot's health, flight safety, and completion of the mission. Only those candidates with the highest psychophysical score are accepted to undergo special aeromedical screening. Physical suitability is an important factor in the selection and classification of candidates for flight training programs, and pulmonary function testing is central within this screening protocol. METHODS: We developed a respiratory algorithm for this unique screening process. The algorithm represents a practical and efficient approach for large-scale screening of healthy candidates for flight training. The algorithm deals with the major pulmonary health problems encountered in a previously screened healthy population aged 17 to 25 years. If by anamnesis, physical examination results, or baseline spirometry findings there is reason to suspect a respiratory problem that could emerge to endanger the pilot's life, a specially designed evaluation is performed according to the algorithm. We explain, step by step, the basis for each suggested test in order to reach a decision (operational specifications). The pulmonary function studies we recommend are reasonably priced and can be easily and reliably performed by regular medical staff technicians. The major justification for performing pulmonary function studies in a healthy population that has already gone through a preliminary medical screening and has been found fit is to identify occult or latent abnormalities. These abnormalities may have no or minimal clinical expression under ordinary circumstances but, under the stress of flight during the ensuing 5 to 10 years, may produce serious limitation in function. RESULTS: Two cases, seen in the Air Force Medical Center, are presented to illustrate how the algorithm is implemented. The algorithm has been in use for more than 5 years, and has been applied to the screening of several thousand candidates. Follow-up of the accepted candidates has not revealed any significant defects in the decision-making process. CONCLUSION: Use of the algorithm is highly cost-effective since it allows for nonspecialist physicians to carry out pulmonary screening and involves the pulmonary specialist only infrequently, ie, when a particularly complicated and/or borderline case is encountered. It is our contention that a similar algorithm would be useful in many other settings where large-scale screening is required.
Asunto(s)
Medicina Aeroespacial , Algoritmos , Personal Militar , Pruebas de Función Respiratoria/métodos , Adolescente , Adulto , Análisis Costo-Beneficio , Humanos , Israel , Masculino , Pruebas de Función Respiratoria/economíaRESUMEN
A nonsmoker drill polisher with interstitial lung disease is presented. The environmental exposure was mainly to aluminum oxide, aluminum silicate, and hard metals. Bronchoalveolar lavage revealed high eosinophilia, and transbronchial biopsy specimen disclosed interstitial pneumonia with giant cell infiltrates and peribronchiolar accumulation of macrophages laden with opaque dust. Mineralogic studies done from the tissue revealed a high concentration of exogenous particles that were identified as hard metals and aluminum silicate. These findings are compatible with hard metal pneumoconiosis.
Asunto(s)
Metales , Enfermedades Profesionales/etiología , Neumoconiosis/etiología , Eosinofilia Pulmonar/etiología , Compuestos de Aluminio , Líquido del Lavado Bronquioalveolar/citología , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Profesionales/patología , Neumoconiosis/patología , Eosinofilia Pulmonar/patologíaRESUMEN
A double-blind, randomized, crossover chronic study was done to determine the efficacy of colchicine in 10 atopic patients with asthma. A constant dose of sustained-release theophylline and albuterol by inhalation, as needed, was administered. Compared to placebo, colchicine, 0.5 mg twice daily, significantly reduced the mean (+/- SEM) daily clinical score from 2.18 +/- 0.34 to 1.64 +/- 0.32 (p less than 0.05), and the daily number of inhalations of albuterol from 5.89 +/- 1.48 to 4.01 +/- 1.26 (p less than 0.02). Colchicine significantly (p less than 0.05) increased the concanavalin A-induced suppressor cell function from 16.2 +/- 4.6% to 39.0 +/- 10.7%, which was similar to healthy volunteers (41.1 +/- 3.5%). Furthermore, colchicine significantly (p less than 0.05) decreased serum IgE from 248 +/- 63 to 188 +/- 46 IU/ml. Colchicine had no significant effect on pulmonary function tests, the early phase reaction of antigen-induced bronchial inhalation challenge, and immediate skin test responses. Thus, colchicine has immunomodulatory effects that may perhaps have a mild benefit in the treatment of asthma.