RESUMEN
Ethylene dibromide was administered intragastrically on 14 consecutive days to B6C3F1 female mice. Host resistance was not altered after challenge with B16F10 tumor cells, Listeria monocytogenes, influenza, or Herpes simplex viruses. In contrast, decreases were seen in relative thymus and spleen weights, red blood cells, hemoglobin, hematocrit, and in alveolar macrophage, natural killer cell, T-cell, and mixed lymphocyte culture responses. Increases occurred in relative kidney and liver weights, cholesterol, peripheral neutrophils, resident peritoneal exudate cells (with increased phagocytosis) and plaque-forming cells. There was little difference between the dose that caused immune modulation and that which produced significant toxicity.
Asunto(s)
Citotoxicidad Inmunológica/efectos de los fármacos , Dibromuro de Etileno/toxicidad , Células Asesinas Naturales/inmunología , Activación de Linfocitos , Macrófagos Peritoneales/inmunología , Melanoma Experimental/inmunología , Análisis de Varianza , Animales , Proteínas Sanguíneas/efectos de los fármacos , Proteínas Sanguíneas/metabolismo , Peso Corporal/efectos de los fármacos , Susceptibilidad a Enfermedades , Relación Dosis-Respuesta a Droga , Enzimas/sangre , Femenino , Herpes Simple/inmunología , Células Asesinas Naturales/efectos de los fármacos , Klebsiella pneumoniae/patogenicidad , Listeriosis/inmunología , Pulmón/efectos de los fármacos , Pulmón/microbiología , Activación de Linfocitos/efectos de los fármacos , Prueba de Cultivo Mixto de Linfocitos , Macrófagos Peritoneales/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Tamaño de los Órganos/efectos de los fármacos , Infecciones por Orthomyxoviridae/inmunologíaRESUMEN
Pulmonary infections may be induced in experimental animals by using several exposure routes. Inhalation of microbial aerosols is often viewed as the most relevant exposure route, although the comparability of either intranasal (i.n.) or intratracheal (i.t.) inoculation to aerosol inhalation is unclear. In these studies, the infection of mice with either Streptococcus zooepidemicus or influenza virus was compared following i.n., i.t., or aerosol challenge. The 50% lethal dose was determined by each exposure route for both microbes, and the organ clearance of a 50% lethal dose was determined. Mice were as or more sensitive to bacterial or viral infection following i.n. or i.t. instillation as compared with aerosol challenge. Organ clearance patterns of virus or bacteria varied slightly with exposure route.
Asunto(s)
Virus de la Influenza A/patogenicidad , Streptococcus/patogenicidad , Aerosoles , Animales , Femenino , Inyecciones , Dosificación Letal Mediana , Masculino , Ratones , Ratones Endogámicos , Infecciones por Orthomyxoviridae/etiología , Sepsis/etiología , Factores Sexuales , Vísceras/microbiologíaRESUMEN
Various health effect parameters were compared to determine which tests were the most sensitive indicators of toxic effects of exposure to metallic sulfate aerosols. Inhalation studies were conducted involving either single 3-hr exposure to various concentrations of cupric sulfate (0.43-2.64 mg/m3 SO4), aluminum sulfate (1.65-2.75 mg/m3 SO4), and aluminum ammonium sulfate (1.47-3.81 mg/m3 SO4) or multiple (five and ten) daily 3-hr exposures to cupric sulfate (0.1 mg/m3 SO4). The test parameters studied in male and female CD1 mice were changes in mortality after respiratory infection with Group C Streptococcus zooepidemicus; pulmonary bactericidal activity; pulmonary cell number, type, viability, and ATP content; and pulmonary morphology by scanning electron microscopy. Tracheal ciliary beating frequency and morphology were also studied in both CD1 mice and Syrian golden hamsters. Differences in bacteria-induced mortality rate appeared to be the most sensitive and consistent indicators of pollutant damage. The other parameters produced evidence of damage but generally only at the higher pollutant concentrations. Cupric sulfate was the most toxic of the three sulfates, but the differences between the toxicity of the aluminum sulfate and aluminum ammonium sulfate were less clear.
Asunto(s)
Contaminantes Atmosféricos/toxicidad , Compuestos de Alumbre/toxicidad , Aluminio/toxicidad , Cobre/toxicidad , Sulfatos/toxicidad , Adenosina Trifosfato/análisis , Administración por Inhalación , Animales , Infecciones Bacterianas/inmunología , Sulfato de Cobre , Cricetinae , Epitelio/efectos de los fármacos , Femenino , Pulmón/efectos de los fármacos , Masculino , Mesocricetus , Ratones , Microscopía Electrónica de Rastreo , Tráquea/efectos de los fármacos , Tráquea/ultraestructuraRESUMEN
Adult female B6C3F1 mice received distilled water only or water containing 10, 50, or 250 ppm of cadmium chloride (CdCl2) for 90 days. Body weights were measured weekly. On selected days during exposure and on Day 91, Cd tissue concentrations were measured along with changes in primary antibody responses. On Day 91 mice also received a primary challenge with various infectious agents. T- and B-cell mitogenesis, natural killer (NK) cell function, delayed type hypersensitivity (DTH) as well as macrophage bactericidal activity, and phagocytosis were measured. There was no change in body weight gain, organ weights, or in humoral immunity during treatment even though cadmium had accumulated in significant quantities in the tissues. Compared with controls, exposure to cadmium had no statistically significant effect on mortality and mean survival time following primary or secondary challenge with any of the infectious agents. However, there was a dose-related, increased susceptibility to Herpes simplex type 2 virus. T- and B-lymphocyte proliferation was significantly reduced, and macrophage phagocytosis was significantly increased following cadmium exposure. NK cell activity was augmented, but not significantly. Macrophage bactericidal activity and DTH were not significantly altered.
Asunto(s)
Intoxicación por Cadmio/inmunología , Sistema Inmunológico/efectos de los fármacos , Animales , Formación de Anticuerpos , Peso Corporal , Femenino , Hipersensibilidad Tardía , Inmunidad Innata , Riñón/metabolismo , Células Asesinas Naturales/inmunología , Activación de Linfocitos , Macrófagos/efectos de los fármacos , Macrófagos/fisiología , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Tamaño de los Órganos , Ovinos , Bazo/metabolismo , Timo/metabolismoRESUMEN
Mice exposed 5 h/d, 5 d/wk up to 103 d, to 0.2 mg O3/m3 or to a mixture of O3, 13.2 mg SO2/m3, and 1.04 mg (NH4)2SO4 aerosol/m3 showed significantly greater susceptibility to group C streptococcal aerosol infection relative to filtered air controls. Pulmonary bactericidal activity by alveolar macrophages was significantly enhanced in the lungs of mice exposed to the mixture relative to those inhaling filtered air or O3 alone. The total number and distribution of the free cells lavaged from the lungs, as well as cellular ATP levels, did not change due to the pollutant exposures. In vitro cytostasis in tumor target cells cocultured with peritoneal macrophages from the exposed mice was significantly enhanced in the O3-exposed and in the mixture-exposed treatment groups relative to controls and also in the mixture-exposed relative to the O3-exposed group when a target-to-effector-cell ratio of 1:10 was used; no such effects were observed when this ratio was 1:20. Splenic T-lymphocyte function, as measured by blastogenesis to mitogens and alloantigens, was affected by exposure to O3 and/or the mixture, although the patterns of effects were qualitatively different. Splenic B-cell function and macrophage antigen processing, as measured by the generation of antibody plaque-forming cells, was unaffected by exposure.
Asunto(s)
Sulfato de Amonio/inmunología , Inmunidad Celular/efectos de los fármacos , Ozono/inmunología , Dióxido de Azufre/inmunología , Aerosoles , Contaminantes Atmosféricos/toxicidad , Animales , Cámaras de Exposición Atmosférica , Femenino , Técnicas In Vitro , Infecciones por Klebsiella/inmunología , Klebsiella pneumoniae , Pulmón/efectos de los fármacos , Pulmón/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Ratones , Ratones Endogámicos , Infecciones Estreptocócicas/inmunología , Factores de TiempoRESUMEN
As part of a program to develop and validate methodology to measure chemically induced immunotoxicity, the effect of DES on resistance of adult B6C3F1 female mice to various microorganisms and to challenge with syngeneic tumor cells was evaluated. The mice received sc injections of 50 microliter corn oil alone or of corn oil containing the equivalent of 0.2, 1, and 4 mg DES/kg X d for 14 d. Three days later they were challenged with Listeria monocytogenes, Streptococcus sp. influenza virus, herpes virus, Trichinella spiralis, or B16-F10 tumor cells. Host resistance parameters were mortality for the bacterial and viral systems, expulsion of adult parasites from the gut for T. spiralis, and lung weights for the B16-F10 tumor-cell model. Host resistance to L. monocytogenes, herpes virus, and T. spiralis was significantly decreased following DES exposure. Resistance to Streptococcus sp. was decreased, but not at a statistically significant level following these doses of DES. However a dose of DES at 8 mg/kg X d resulted in a highly significant decrease in resistance to the organism. Resistance to influenza virus was unaffected by the DES. In contrast to the above, host resistance to iv-administered B16-F10 tumor cells was significantly increased as a consequence of DES exposure. These model systems for measuring alterations in host resistance have been indicated to hold potential for the routine screening of drugs, chemicals, and environmental agents for their possible immune effects, both adverse and potentiating. The results indicate the importance of selecting the appropriate assay for evaluating a particular agent. They also stress the necessity for including host resistance assays along with assays to measure specific immune aspects, in order to assess in the intact animal the overall effect of complex immune interactions following exposure to a test agent.
Asunto(s)
Dietilestilbestrol/toxicidad , Inmunidad/efectos de los fármacos , Infecciones/inmunología , Neoplasias Experimentales/inmunología , Animales , Femenino , Herpes Simple/inmunología , Listeriosis/inmunología , Melanoma/inmunología , Ratones , Ratones Endogámicos , Infecciones por Orthomyxoviridae/inmunología , Infecciones Estreptocócicas/inmunología , Triquinelosis/inmunologíaRESUMEN
A significant increase in mortality due to acute respiratory pneumonia caused by inhalation of Streptococcus pyogenes aerosol was seen after a single 3-h exposure of mice to 14.8-28.4 mg/m3 peroxyacetyl nitrate (PAN). The excess mortality ranged from 8 to 39% and the decrease in survival time from 2.4 to 7.9 d. A single exposure to 25.0 mg/m3 PAN resulted in a significant increase in total number of cells lavaged from the lungs but somewhat decreased levels of adenosine triphosphate (ATP) in alveolar macrophages. Exposure to 7.4 mg/m3 PAN for 3 h/d, 5 d/wk, for 2 wk resulted in a reduced total count of free pulmonary cells and a significant reduction of ATP levels in alveolar macrophages but had no effect on mortality or survival rate. Scanning electron microscopic observations of the respiratory tract after both single and multiple exposures to PAN showed raised and sloughing nonciliated cells in the nasal cavities and tracheas and presence of excess mucus. Six daily 3-h exposures to 25.0 mg/m3 PAN did not produce any marked changes in a chronic respiratory infection in mice as measured by Mycobacterium tuberculosis lung titers.
Asunto(s)
Acetatos/toxicidad , Contaminantes Atmosféricos/toxicidad , Infecciones Bacterianas/inmunología , Ácido Peracético/toxicidad , Infecciones del Sistema Respiratorio/inmunología , Animales , Femenino , Inmunidad Innata/efectos de los fármacos , Pulmón/efectos de los fármacos , Pulmón/microbiología , Ratones , Ratones Endogámicos , Nitratos/toxicidad , Ácido Peracético/análogos & derivados , Neumonía/inmunología , Sistema Respiratorio/patología , Infecciones Estreptocócicas/inmunología , Tuberculosis Pulmonar/inmunologíaRESUMEN
Exposure of mice to 1.96 mg/m3 ozone (O3) 3 h/day, 5 days/week, for up to 8 weeks beginning at 1 or 2 weeks after challenge with Mycobacterium tuberculosis R1Rv resulted in significant enhancement of bacterial titers in the lungs at 5 through 8 weeks after challenge when compared to mice exposed to filtered air. Exposure to lower concentrations of O3 did not produce any significant changes compared to controls. Exposure of guinea pigs to 2.9 mg/m3O3 for 3 h immediately after challenge with M. tuberculosis resulted in a suppression of the cutaneous delayed hypersensitivity response, without affecting the serum hemagglutination antibody titers. However, exposure of guinea pigs to 0.98 mg/m3 O3 3h/day for 5 days, initiated within 3 h after the infectious challenge, enhanced hemagglutination antibody titers initially, but the delayed hypersensitivity reaction did not differ from controls.
Asunto(s)
Ozono/toxicidad , Tuberculosis Pulmonar/inmunología , Animales , Femenino , Cobayas , Pulmón/microbiología , Ratones , Ratones Endogámicos C57BL , Factores de Tiempo , Tuberculosis Pulmonar/microbiologíaAsunto(s)
Contaminantes Atmosféricos/toxicidad , Carbono/toxicidad , Ácidos Sulfúricos/toxicidad , Tráquea/efectos de los fármacos , Animales , Carbono/administración & dosificación , Cilios/efectos de los fármacos , Cricetinae , Epitelio/efectos de los fármacos , Mesocricetus , Técnicas de Cultivo de Órganos , Ácidos Sulfúricos/administración & dosificación , Tráquea/ultraestructuraAsunto(s)
Carbono/toxicidad , Inmunidad/efectos de los fármacos , Infecciones del Sistema Respiratorio/etiología , Ácidos Sulfúricos/toxicidad , Aerosoles , Animales , Carbono/administración & dosificación , Masculino , Ratones , Neumonía Viral/etiología , Sistema Respiratorio/efectos de los fármacos , Sistema Respiratorio/ultraestructura , Ácidos Sulfúricos/administración & dosificación , Factores de TiempoAsunto(s)
Dióxido de Nitrógeno/farmacología , Ozono/farmacología , Animales , Femenino , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/fisiopatología , Klebsiella pneumoniae , Pulmón/microbiología , Ratones , Ratones Endogámicos , Infecciones Estreptocócicas/microbiología , Infecciones Estreptocócicas/fisiopatología , Factores de TiempoAsunto(s)
Formación de Anticuerpos/efectos de los fármacos , Exposición a Riesgos Ambientales , Dióxido de Nitrógeno/farmacología , Animales , Anticuerpos/análisis , Pruebas de Inhibición de Hemaglutinación , Inmunoglobulinas/análisis , Vacunas contra la Influenza , Ratones , Pruebas de Neutralización , VacunaciónAsunto(s)
Formación de Anticuerpos , Reacciones Antígeno-Anticuerpo , Dióxido de Nitrógeno/farmacología , Orthomyxoviridae/inmunología , Animales , Antígenos Virales , Bronquios/efectos de los fármacos , Exposición a Riesgos Ambientales , Eritrocitos/efectos de los fármacos , Haplorrinos , Pruebas de Inhibición de Hemaglutinación , Pruebas de Hemaglutinación , Pulmón/efectos de los fármacos , Pulmón/patología , Masculino , Microscopía Electrónica , Enfisema Pulmonar/inducido químicamente , Pruebas de Función RespiratoriaAsunto(s)
Formación de Anticuerpos , Dióxido de Nitrógeno , Orthomyxoviridae , Animales , Anticuerpos/análisis , Temperatura Corporal , Exposición a Riesgos Ambientales , Haplorrinos , Pruebas de Inhibición de Hemaglutinación , Pruebas de Hemaglutinación , Hematócrito , Inyecciones , Pulmón/patología , Masculino , Pruebas de Neutralización , Edema Pulmonar/patología , Especificidad de la Especie , Espirometría , TráqueaRESUMEN
The immunogenic response of mice vaccinated intranasally or subcutaneously with increasing doses of a purified, concentrated intact A(2)/Taiwan influenza vaccine or its Tween-ether derived vaccines was compared. Immunogenicity was measured by serum neutralization and hemagglutination-inhibition antibodies, lung lesions scores, and protection against respiratory challenge with live airborne influenza virus. Intact (untreated) vaccine, Tween-ether-treated (ET) vaccine, and the isolated hemagglutinins (HA) provided protection and stimulated homologous antibody response at the 35- and 70-chicken cell agglutination (CCA) unit level. At a lower dosage level, the vaccines administered by the subcutaneous route appeared to confer better protection. The ET vaccine was superior to intact virus or HA vaccines when administered subcutaneously. The minimum amount of the HA and intact vaccine given subcutaneously that protected mice against respiratory challenge was 7 CCA units (3.5 units injected twice) compared to 0.7 CCA units (0.35 units injected twice) for the ET vaccine. No heterologous antibody to the A/PR/8/34 or B/Mass/3/66 was noted. Low-level serum-neutralizing antibody was found against the A(2)/Japan/170 strain but, despite high levels of homologous A(2)/Taiwan/64 antibody, no cross-reactivity was found with the recent A(2)/Hong Kong/68 variant.
Asunto(s)
Pruebas de Aglutinación , Animales , Formación de AnticuerposRESUMEN
A sensitive, reliable plaque assay system is described for five rhinoviruses using freshly prepared methylcellulose overlay and human embryonic diploid cells. Circular plaques with irregular edges, 2 mm in size, were formed by rhinoviruses 1A, 2, 6, and 13 after 6 or 7 days of incubation. A fifth rhinovirus, 17, formed a 1- to 2-mm feather plaque after 14 days of incubation. Plaque counts of rhinoviruses 1A and 13 were not affected by varying the pH of the overlay from 6.9 to 7.5. Plaque sizes and plaque-forming unit values of high passage rhinoviruses 1A and 13 were equivalent when tested at 26, 31, or 36 C. The rhinoviruses tested were sensitive to incubation at 40 C or heating at 50 C. Enhancement of plaques was observed when Mg(++) was incorporated into agar overlays, but enhancement did not occur when Mg(++) was added to methylcellulose overlays.
Asunto(s)
Técnicas de Cultivo , Efecto Citopatogénico Viral , Metilcelulosa , Rhinovirus/aislamiento & purificación , Humanos , Concentración de Iones de Hidrógeno , Magnesio/farmacología , Métodos , Pruebas de Neutralización , TemperaturaRESUMEN
This paper reports the use of zonal ultracentrifuge techniques to conduct biophysical studies of rhinoviruses grown with WI-38 cells. Good clean-out of infectivity from rhinovirus harvests was obtained with the continuous-flow B-V and B-IX rotors. Use of the B-V rotor resulted in the successful concentration of rhinovirus infectivity and antigenicity. Additional purification was achieved by the combined use of continuous-flow centrifugation and isopycnic banding procedures. Two particle sizes were found to be associated with the virus-infected cell harvests. The infectious 22-nm particle banded in density ranges of 1.38 to 1.40 g/cm(3) in CsCl and 1.26 to 1.27 g/cm(3) in potassium citrate. The 8.0 nm capsomere was composed of 2.0 nm subunits and banded with a density of protein at 1.28 g/cm(3) in CsCl. Equivalent sedimentation coefficients of 155 or 185, depending on particle density in sucrose, were calculated from rate zonal experiments by use of the B-IV zonal rotor.
Asunto(s)
Centrifugación Zonal , Rhinovirus/aislamiento & purificación , Centrifugación por Gradiente de Densidad , Cesio , Cloruros , Citratos , Técnicas de Cultivo , Embrión de Mamíferos , Humanos , Métodos , Microscopía Electrónica , Potasio , Rhinovirus/crecimiento & desarrollo , Rhinovirus/inmunología , Sacarosa , Replicación ViralRESUMEN
The addition of 10 hemolytic units of guinea pig complement has been shown to enhance the neutralizing capacity of respiratory syncytial (RS) immune sera produced in guinea pigs and ferrets. This same immune sera, when tested without complement, had little or no neutralizing capacity. The addition of complement to RS immune horse serum did not significantly increase its neutralizing capacity. Immune horse serum effectively neutralized RS virus without complement. Other studies indicated that a 50% tissue culture infective dose of between 30 and 100 should be used in RS serum neutralization tests and that incubation should be for 90 to 105 min at room temperature. The neutralizing capacity of guinea pig immune serum was not increased by the use of filtered virus. The rate of virus neutralization, however, was increased with the addition of 10 hemolytic units of complement. The neutralizing capacity of RS immune horse serum was much greater for filtered than for unfiltered RS virus. The addition of complement increased the rate of virus neutralization but did not increase the neutralizing capacity of the horse immune serum.