Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 4 de 4
Filtrar
Más filtros

Métodos Terapéuticos y Terapias MTCI
Bases de datos
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
J Immunol ; 167(11): 6583-92, 2001 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-11714828

RESUMEN

IL-13 has emerged as a major contributor to allergic and asthmatic responses, and as such it represents an attractive target in these diseases. In this study, IL-13-responsive cells in the lung were targeted via the intranasal administration of IL-13-PE38QQR (IL-13-PE), comprised of human IL-13 and a derivative of Pseudomonas exotoxin, to Aspergillus fumigatus-sensitized mice challenged with A. fumigatus spores, or conidia. Mice received 50, 100, or 200 ng of IL-13-PE or diluent alone (i.e., control group) on alternate days from day 14 to day 28 after the conidia challenge. The control group of mice exhibited significant airway hyperreactivity, goblet cell hyperplasia, and peribronchial fibrosis at day 28 after conidia. Although the two lower doses of IL-13-PE had limited therapeutic effects in mice with fungal-induced allergic airway disease, the highest dose of IL-13-PE tested significantly reduced all features of airway disease compared with the control group. Whole lung mRNA expression of IL-4Ralpha and IL-13Ralpha1 was markedly reduced, whereas bronchoalveolar lavage and whole lung levels of IFN-gamma were significantly elevated in mice treated with 200 ng of IL-13-PE compared with the control group. This study demonstrates that a therapy designed to target IL-13-responsive cells in the lung ameliorates established fungal-induced allergic airway disease in mice.


Asunto(s)
ADP Ribosa Transferasas , Aspergilosis Broncopulmonar Alérgica/terapia , Toxinas Bacterianas/genética , Toxinas Bacterianas/inmunología , Exotoxinas/genética , Exotoxinas/inmunología , Interleucina-13/genética , Interleucina-13/inmunología , Proteínas Recombinantes de Fusión/inmunología , Factores de Virulencia , Adyuvantes Inmunológicos/uso terapéutico , Administración Intranasal , Animales , Aspergilosis Broncopulmonar Alérgica/inmunología , Aspergilosis Broncopulmonar Alérgica/patología , Toxinas Bacterianas/administración & dosificación , Hiperreactividad Bronquial/inmunología , Hiperreactividad Bronquial/terapia , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Enfermedad Crónica , Relación Dosis-Respuesta Inmunológica , Exotoxinas/administración & dosificación , Femenino , Fibrosis , Células Caliciformes/patología , Humanos , Hiperplasia , Inmunoglobulina E/biosíntesis , Inmunoglobulina E/sangre , Inmunoglobulina G/biosíntesis , Inflamación/inmunología , Inflamación/terapia , Interferón gamma/biosíntesis , Interleucina-12/biosíntesis , Interleucina-13/administración & dosificación , Interleucina-13/biosíntesis , Subunidad alfa1 del Receptor de Interleucina-13 , Interleucina-4/biosíntesis , Pulmón/inmunología , Pulmón/metabolismo , Pulmón/patología , Recuento de Linfocitos , Ratones , Ratones Endogámicos CBA , Proyectos Piloto , Pseudomonas aeruginosa/inmunología , ARN Mensajero/antagonistas & inhibidores , ARN Mensajero/biosíntesis , Receptores de Interleucina/antagonistas & inhibidores , Receptores de Interleucina/genética , Receptores de Interleucina-13 , Receptores de Interleucina-4/antagonistas & inhibidores , Receptores de Interleucina-4/genética , Proteínas Recombinantes de Fusión/administración & dosificación , Linfocitos T/patología , Exotoxina A de Pseudomonas aeruginosa
2.
Br J Pharmacol ; 134(6): 1166-79, 2001 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11704636

RESUMEN

1. Chemokine expression and function was monitored in an experimental model of granulomatous tissue formation after injection of croton oil in complete Freund's adjuvant (CO/CFA) into mouse dorsal air-pouches up to 28 days. 2. In the first week, mast cell degranulation and leukocyte influx (mononuclear cell, MNC, and polymorphonuclear cell, PMN) were associated with CXCR2, KC and macrophage inflammatory protein (MIP)-2 mRNA expression, as determined by TaqMan reverse transcriptase-polymerase chain reaction. KC ( approximately 400 pg x mg protein(-1), n=12) and MIP-2 (approximately 800 pg x mg protein(-1), n=12) proteins peaked at day 7, together with myeloperoxidase (MPO) activity. Highest MIP-1alpha (>1 ng x mg protein(-1), n=12) levels were measured at day 3. 3. After day 7, a gradual increase in CCR2 and CCR5 mRNA, monocyte chemoattractant protein (MCP)-1 mRNA and protein expression was measured. MCP-1 protein peaked at day 21 (approximately 150 pg x mg protein(-1), n=12) and was predominantly expressed by mast cells. A gradual increase in N-acetyl-beta-D-glucosaminidase (NAG) activity (maximal at 28 days) was also measured. 4. An antiserum against MIP-1alpha did not modify the inflammatory response measured at day 7 (except for a 50% reduction in MIP-1alpha levels), but provoked a significant increase in MPO, NAG and MCP-1 levels as measured at day 21 (n=6, P<0.05). An antiserum to MCP-1 reduced NAG activity at day 21 but increased MPO activity values (n=8, P<0.05). 5. In conclusion, we have shown that CO/CFA initiates a complex inflammatory reaction in which initial expression of MIP-1alpha serves a protective role whereas delayed expression of MCP-1 seems to have a genuine pro-inflammatory role.


Asunto(s)
Quimiocina CCL2/fisiología , Quimiocinas/biosíntesis , Proteínas Inflamatorias de Macrófagos/fisiología , Receptores de Quimiocina/biosíntesis , Animales , Quimiocina CCL2/biosíntesis , Quimiocina CCL2/genética , Quimiocina CCL3 , Quimiocina CCL4 , Quimiocinas/genética , Aceite de Crotón/farmacología , Modelos Animales de Enfermedad , Femenino , Adyuvante de Freund/farmacocinética , Inmunohistoquímica , Inflamación/tratamiento farmacológico , Leucocitos/inmunología , Proteínas Inflamatorias de Macrófagos/biosíntesis , Proteínas Inflamatorias de Macrófagos/genética , Mastocitos/efectos de los fármacos , Ratones , Peroxidasa/biosíntesis , Peroxidasa/genética , Peroxidasa/fisiología , ARN Mensajero/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo
3.
J Immunol ; 166(8): 5219-24, 2001 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-11290806

RESUMEN

IL-13 and IL-4 are key contributors to the asthmatic phenotype. The temporal role of these cytokines in airway function, inflammation, and remodeling were assessed in a chronic murine model of Asperigillus fumigatus-induced allergic asthma. IL-13 and IL-4 protein levels were significantly elevated by 30 days after conidia challenge in A. fumigatus-sensitized mice. Furthermore, IL-13Ralpha1 mRNA expression was significantly elevated 7 days after conidia challenge and remained elevated until day 21. In contrast, IL-13Ralpha2 mRNA expression, although constitutively expressed in naive lung, was absent in the lungs of A. fumigatus-sensitized mice both before and after conidia challenge. Membrane-bound IL-4R mRNA expression was significantly elevated 7 days after conidia challenge; however, soluble IL-4R mRNA expression was increased 30 days after conidia challenge. Immunoneutralization of IL-13 between days 14 and 30 or days 30 and 38 after fungal sensitization and challenge significantly attenuated airway hyperresponsiveness, collagen deposition, and goblet cell hyperplasia at day 38 after conidia challenge; however, the effects of IL-4 immunoneutralization during the same time periods were not as marked. IFN-gamma and IL-12 release after Aspergillus Ag restimulation was elevated from spleen cells isolated from mice treated with IL-4 anti-serum compared with IL-13 anti-serum or normal rabbit serum-treated mice. This study demonstrates a pronounced therapeutic effect of IL-13-immunoneutralization at extended time points following the induction of chronic asthma. Most importantly, these therapeutic effects were not reversed following cessation of treatment, and IL-13 anti-serum treatment did not alter the systemic immune response to Ag restimulation, unlike IL-4 immunoneutralization. Therefore, IL-13 provides an attractive therapeutic target in allergic asthma.


Asunto(s)
Asma/inmunología , Asma/terapia , Interleucina-13/inmunología , Interleucina-13/uso terapéutico , Animales , Antígenos Fúngicos/administración & dosificación , Aspergillus fumigatus/inmunología , Asma/patología , Asma/fisiopatología , Hiperreactividad Bronquial/inmunología , Hiperreactividad Bronquial/patología , Hiperreactividad Bronquial/fisiopatología , Enfermedad Crónica , Colágeno/antagonistas & inhibidores , Colágeno/metabolismo , Citocinas/metabolismo , Células Caliciformes/patología , Hiperplasia , Sueros Inmunes/administración & dosificación , Inyecciones Intraperitoneales , Interleucina-13/antagonistas & inhibidores , Interleucina-13/biosíntesis , Subunidad alfa1 del Receptor de Interleucina-13 , Interleucina-4/antagonistas & inhibidores , Interleucina-4/biosíntesis , Interleucina-4/inmunología , Pulmón/inmunología , Pulmón/metabolismo , Activación de Linfocitos , Ratones , Ratones Endogámicos CBA , Fibrosis Pulmonar/inmunología , Fibrosis Pulmonar/prevención & control , ARN Mensajero/biosíntesis , Receptores de Interleucina/biosíntesis , Receptores de Interleucina/genética , Receptores de Interleucina-13 , Receptores de Interleucina-4/biosíntesis , Receptores de Interleucina-4/genética , Bazo/citología , Bazo/inmunología , Bazo/metabolismo , Esporas Fúngicas/inmunología , Factores de Tiempo
4.
Inflamm Res ; 49(6): 297-304, 2000 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10939620

RESUMEN

OBJECTIVE AND DESIGN: This study examined the role of nitric oxide in changes in airway physiology and inflammation in a murine model of fungal allergy induced by Aspergillus fumigatus (A. fumigatus) by treatment of A. fumigatus-sensitized mice with NG-nitro-L-arginine methyl ester (L-NAME) or D-NAME (8 mg/kg; i.p.). MATERIALS AND METHODS: Female CBA/J mice received A. fumigatus antigen dissolved in incomplete Freund's adjuvant (10 mg/100 ml i.p. and s.c.) followed 2 weeks later by A. fumigatus antigens (20 mg; i.n.) and a subsequent i.t. challenge 4 days later. Airway physiology and inflammation were examined (24 to 72 h) following i.t. challenge. RESULTS: L-NAME-treated mice had lower lung nitrite levels 24 h after A. fumigatus challenge, but higher airway hyperresponsiveness and inflammation compared to D-NAME controls. Airway inflammation in the L-NAME treatment group (72 h) was characterized by a greater bronchoalveolar lavage (BAL), peribronchial eosinophilia and augmented levels of CC chemokines compared to controls. CONCLUSIONS: These findings suggest that nitric oxide is an important modulator of airway hyperresponsiveness, inflammation and C-C chemokine generation during allergic airway responses to A. fumigatus.


Asunto(s)
Aspergillus fumigatus/inmunología , Asma/fisiopatología , Hiperreactividad Bronquial/etiología , Quimiocinas CC/biosíntesis , Eosinofilia/etiología , Óxido Nítrico/fisiología , Animales , Femenino , Inmunoglobulina E/sangre , Ratones , Ratones Endogámicos CBA , NG-Nitroarginina Metil Éster/farmacología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA