RESUMEN
Angiotensin-converting enzyme (ACE) inhibitors have non-hemodynamic, pleiotropic effects on the immune response. The effects of ACE inhibitors on the production of cytokines and T-cell functions are well established. However, little is known on the effects of these medicines on humoral response to foreign antigens. In this study, we investigated the effect of enalapril treatment on ovalbumin (OVA)-specific IgG1 and IgG2c production in mice determined by ELISA. Two groups of 8-week-old C57BL/6 females mice (3-4/group) were subcutaneously immunized with OVA (10 µg/animal) in presence of Alhydrogel (1 mg/mouse) and boosted at day 21. The mice were treated with enalapril (5 mg/kg daily, po) or were left without treatment for one month. The animals were bled from the orbital plexus on days 0, 7, 14, 21, and 28 after the first immunization and the sera were stored at -20°C until usage. OVA-specific serum IgG1 and IgG2c were determined by ELISA using serum from each individual animal. The results showed that enalapril significantly increased anti-OVA serum IgG2c in the secondary response without affecting IgG1 synthesis. These data expand our understanding on the properties of enalapril on the immune response, including antibody production.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Enalapril/farmacología , Inmunidad Humoral/efectos de los fármacos , Inmunoglobulina G/sangre , Ovalbúmina/inmunología , Animales , Formación de Anticuerpos/efectos de los fármacos , Femenino , Inmunoglobulina G/inmunología , Ratones Endogámicos C57BL , Modelos Animales , Células TH1/inmunología , Células Th2/inmunologíaRESUMEN
Angiotensin-converting enzyme (ACE) inhibitors have non-hemodynamic, pleiotropic effects on the immune response. The effects of ACE inhibitors on the production of cytokines and T-cell functions are well established. However, little is known on the effects of these medicines on humoral response to foreign antigens. In this study, we investigated the effect of enalapril treatment on ovalbumin (OVA)-specific IgG1 and IgG2c production in mice determined by ELISA. Two groups of 8-week-old C57BL/6 females mice (3–4/group) were subcutaneously immunized with OVA (10 μg/animal) in presence of Alhydrogel (1 mg/mouse) and boosted at day 21. The mice were treated with enalapril (5 mg/kg daily, po) or were left without treatment for one month. The animals were bled from the orbital plexus on days 0, 7, 14, 21, and 28 after the first immunization and the sera were stored at –20°C until usage. OVA-specific serum IgG1 and IgG2c were determined by ELISA using serum from each individual animal. The results showed that enalapril significantly increased anti-OVA serum IgG2c in the secondary response without affecting IgG1 synthesis. These data expand our understanding on the properties of enalapril on the immune response, including antibody production.
Asunto(s)
Animales , Femenino , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Enalapril/farmacología , Inmunidad Humoral/efectos de los fármacos , Inmunoglobulina G/sangre , Ovalbúmina/inmunología , Formación de Anticuerpos/efectos de los fármacos , Inmunoglobulina G/inmunología , Ratones Endogámicos C57BL , Modelos Animales , Células TH1/inmunología , Células Th2/inmunologíaRESUMEN
We previously reported the anti-inflammatory activity of Lafoensia pacari extract in Toxocara canis infection, a model of systemic IL-5-dependent eosinophil migration. In the present study, we describe the kinetics of the anti-inflammatory activity of L. pacari extract and compare it with dexamethasone. T. canis-infected mice were submitted to different treatment protocols and the cells present in bronchoalveolar space and peritoneal cavity were collected at the end of each treatment period. The results showed that L. pacari extract effectively inhibited eosinophil migration only when the treatment was initiated before the peak of eosinophil migration (1st to 18th; 12th to 18th and 12th to 24th day post-infection). When eosinophil migration was established, administration of L. pacari extract had no effect on it (treatment 18th to 24th day post-infection). Dexamethasone was effective in inhibiting eosinophil migration in all periods studied. We suggest that L. pacari extract can potentially be a natural alternative treatment of eosinophilic diseases.
Asunto(s)
Eosinófilos/efectos de los fármacos , Lythraceae/química , Fitoterapia , Extractos Vegetales/uso terapéutico , Toxocariasis/tratamiento farmacológico , Animales , Líquido del Lavado Bronquioalveolar/citología , Movimiento Celular/efectos de los fármacos , Dexametasona/farmacocinética , Dexametasona/farmacología , Dexametasona/uso terapéutico , Eosinófilos/fisiología , Femenino , Hígado/patología , Ratones , Cavidad Peritoneal/citología , Corteza de la Planta/química , Extractos Vegetales/química , Extractos Vegetales/farmacocinética , Distribución Aleatoria , Toxocariasis/patologíaRESUMEN
Toxocariasis is an infection induced by Toxocara canis, an intestinal parasite of dogs. In this study, an experimental murine model of toxocariasis was used to evaluate the anti-inflammatory activity of an ethanolic extract of Lafoensia pacari stem bark. Mice infected with T. canis were treated with L. pacari extract (200 mg/kg, p.o.). Subsequently, we observed a reduction in the number of eosinophils in the peritoneal cavity, bronchoalveolar fluid, blood and bone marrow. Production of interleukin (IL)-5, a major cytokine involved in eosinophilic differentiation, proliferation and activation, is also an important marker for infection. The reduced levels of IL-5 observed in serum, lung homogenates and bronchoalveolar fluid demonstrated the anti-inflammatory mechanisms of L. pacari. Larvae recovery from infected mice treated with L. pacari was comparable with that from untreated mice, suggesting that L. pacari is not toxic to the parasite. Nonetheless, our results demonstrate a potential therapeutic effect of L. pacari extract in IL-5-mediated inflammatory diseases and provide new prospects for the development of drugs to treat IL-5-dependent allergic diseases such as parasite infection and asthma.
Asunto(s)
Interleucina-5/biosíntesis , Magnoliopsida , Fitoterapia , Toxocariasis/tratamiento farmacológico , Animales , Células de la Médula Ósea/inmunología , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Eosinófilos/inmunología , Femenino , Interleucina-5/sangre , Larva , Recuento de Leucocitos , Leucocitos Mononucleares/inmunología , Pulmón/inmunología , Ratones , Cavidad Peritoneal/citología , Extractos Vegetales/uso terapéutico , Toxocariasis/inmunología , Toxocariasis/parasitologíaRESUMEN
The aim of this study was to evaluate the effect of a chemical sclerosing agent, aluminum hydroxide, on pleural remodeling and on respiratory mechanics in rats. Saline (2 mL) or aluminum hydroxide [2 mL (0.15 g/mL)] was instilled intrapleurally in anesthetized male rats. The animals were studied 7 or 30 days after the instillation. Respiratory system, lung, and chest wall elastic, resistive, and viscoelastic/inhomogeneous pressures were measured by the end-inflation occlusion method. We studied the pleural remodeling process by means of semiquantitative analysis of the induced inflammation and quantitative analysis of the collagen extracellular matrix component. The effects on the underlying lung were analyzed morphometrically. Chest wall elastic and viscoelastic pressures increased after aluminum hydroxide instillation independent of time after instillation. Pleural inflammation was observed 7 days after instillation, while pleural adherence with a marked increase in the type I/type III collagen ratio was present 30 days after instillation. Histological examination demonstrated no differences in lung parenchyma among the groups. In conclusion, the present model describes the establishment of pleurodesis by aluminum hydroxide, which thwarts the normal chest wall mechanical profile without inducing any changes in the underlying lungs. The results were disclosed by both mechanical and morphological evaluation of the pleural remodeling.
Asunto(s)
Hidróxido de Aluminio/administración & dosificación , Pleurodesia , Mecánica Respiratoria/efectos de los fármacos , Soluciones Esclerosantes/administración & dosificación , Animales , Elasticidad , Masculino , Pleura/fisiopatología , Ratas , Ratas WistarRESUMEN
We have evaluated the adjuvant action of jacalin, a lectin obtained from seeds of Artocarpus integrifolia, on humoral immune response against the trinitrophenyl (TNP) hapten when conjugated to it and to Trypanosoma cruzi. The protective effect of parasite-specific antibodies generated in mice immunized with epimastigote forms of T. cruzi plus jacalin was also evaluated by determining the parasitemia levels of animals after infection with 1000 trypomastigote forms. Immunization of mice with trinitrophenylated jacalin (TNP-JAC) in saline resulted in an antibody response to the TNP hapten that was eight and 16 times higher than that found in mice immunized with TNP-human gamma globulin (TNP-HGG) or TNP-bovine serum albumin (TNP-BSA), respectively. In addition, immunization with either a lysate or viable epimastigote forms of T. cruzi in the presence of jacalin resulted in a marked increase in the levels of anti-T. cruzi antibodies. The protective action of antibodies against acute infection by T. cruzi was evident when mice were immunized with 1.0 x 10(5) epimastigotes plus jacalin. These animals had a significantly lower parasitemia than those immunized with epimastigotes alone. In contrast, mice immunized with 1.0 x 10(6) epimastigotes developed very low levels of parasitemia, regardless of the presence of jacalin. These data suggest that jacalin is a potent adjuvant in the humoral response to TNP and T. cruzi, and that the protective action of the T. cruzi-specific antibodies depends on the number of parasites used in the immunization protocol.
Asunto(s)
Anticuerpos Antiprotozoarios/sangre , Enfermedad de Chagas/prevención & control , Lectinas/inmunología , Lectinas de Plantas , Trinitrobencenos/inmunología , Trypanosoma cruzi/inmunología , Adyuvantes Inmunológicos , Animales , Femenino , Haptenos/inmunología , Ratones , Ratones Endogámicos BALB C , VacunaciónRESUMEN
Herein, the role of IL-10 in the induction and maintenance of oral tolerance was evaluated. The results show that: (1) mice treated with MoAb anti-IL-10 are permissive to the induction of oral tolerance to OVA; (2) anti-IL-10 treatment did not reverse the in vitro blocking of T cell proliferative response found in orally-tolerized mice; and (3) orally-induced tolerance could not be broken by anti-IL-10 treatment. Taken together, these results suggest that IL-10 is not a fundamental cytokine for the establishment and maintenance of oral tolerance.
Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Tolerancia Inmunológica , Interleucina-10/inmunología , Mucosa Bucal/inmunología , Ovalbúmina/inmunología , Administración Oral , Animales , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática , Inyecciones Intraperitoneales , Ganglios Linfáticos/inmunología , Activación de Linfocitos/inmunología , Ratones , Ratones Endogámicos DBA , Ovalbúmina/administración & dosificación , Linfocitos T/inmunologíaRESUMEN
Immunological memory is embodied in the rapid and enhanced immune responsiveness to previously encountered antigens. Classically, memory would depend on the presence of small resting long-lived specific lymphocytes which, through clonal expansion after priming with antigen, would be present at higher frequencies than in naive animals. Here we report that T-cell-reconstituted athymic mice, which lack recent thymic emigrants, mount a primary response to a T-cell-dependent antigen, but do not develop memory or the capacity to produce specific anti-TNP IgG1 antibodies during the secondary immune response. On the other hand, if thymocytes are continuously provided during the secondary response, a typical secondary immune response is achieved with high levels of specific IgG1. These results lead us to propose that the development of humoral immunological memory cannot be explained solely by the long life span of primed T lymphocytes, but is rather a dynamic state dependent on the continuous presence of recent thymic emigrants and qualitative functional differences in responder T cells.
Asunto(s)
Movimiento Celular/inmunología , Memoria Inmunológica/inmunología , Linfocitos T/inmunología , Timo/inmunología , Animales , Antígenos/inmunología , Células Cultivadas , Femenino , Trasplante de Corazón/inmunología , Inmunoglobulina G/biosíntesis , Interferón gamma/biosíntesis , Interleucina-2/biosíntesis , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Desnudos , Linfocitos T/trasplante , Timo/citología , Trinitrobencenos/inmunologíaRESUMEN
The lectin from Dioclea grandiflora (Mart.) that selectively binds glucose and mannose, when subcutaneously injected in mouse induces an inflammatory cutaneous reaction whose histological analysis reveals an hemorrhagic ulceration with exudative reaction accompanied by an influx of polymorphonuclear leukocytes and giant cells. The presence of lymphocytes and plasma cells in the lesion was insignificant. In order to characterize the in vivo action of inflammatory factors generated by this lesion, distinct lines of mice were used: high and low antibody responder mice; the genetically selected mice to the acute phase of inflammatory reaction; lines of mice deficient in C5, a protein of the complement system. It is shown that the lectin of D. grandiflora acts as an inflammatory agent probably promoting exocytosis and release of mediators
Asunto(s)
Animales , Ratones , Dermatitis por Contacto/patología , Lectinas/toxicidad , Reacción de Fase Aguda , Inyecciones Subcutáneas , Lectinas/administración & dosificación , Factores de TiempoRESUMEN
The lectin from Dioclea grandiflora (Mart.) that selectively binds glucose and mannose, when subcutaneously injected in mouse induces an inflammatory cutaneous reaction whose histological analysis reveals an hemorrhagic ulceration with exudative reaction accompanied by an influx of polymorphonuclear leukocytes and giant cells. The presence of lymphocytes and plasma cells in the lesion was insignificant. In order to characterize the in vivo action of inflammatory factors generated by this lesion, distinct lines of mice were used: high and low antibody responder mice; the genetically selected mice to the acute phase of inflammatory reaction; lines of mice deficient in C5, a protein of the complement system. It is shown that the lectin of D. grandiflora acts as an inflammatory agent probably promoting exocytosis and release of mediators.