RESUMEN
BACKGROUND: Several hydrolyzed cow's milk (CM) formulas are available for avoidance of allergic reactions in CM-allergic children and for prevention of allergy development in high-risk infants. Our aim was to compare CM formulas regarding the presence of immunoreactive CM components, IgE reactivity, allergenic activity, ability to induce T-cell proliferation, and cytokine secretion. METHODS: A blinded analysis of eight CM formulas, one nonhydrolyzed, two partially hydrolyzed (PH), four extensively hydrolyzed (EH), and one amino acid formula, using biochemical techniques and specific antibody probes was conducted. IgE reactivity and allergenic activity of the formulas were tested with sera from CM-allergic patients (n = 26) in RAST-based assays and with rat basophils transfected with the human FcεRI, respectively. The induction of T-cell proliferation and the secretion of cytokines in Peripheral blood mononuclear cell (PBMC) culture from CM allergic patients and nonallergic individuals were assessed. RESULTS: Immune-reactive α-lactalbumin and ß-lactoglobulin were found in the two PH formulas and casein components in one of the EH formulas. One PH formula and the EH formula containing casein components showed remaining IgE reactivity, whereas the other hydrolyzed formulas lacked IgE reactivity. Only two EH formulas and the amino acid formula did not induce T-cell proliferation and proinflammatory cytokine release. The remaining formulas varied regarding the induction of Th2, Th1, and proinflammatory cytokines. CONCLUSION: Our results show that certain CM formulas without allergenic and low proinflammatory properties can be identified and they may also explain different outcomes obtained in clinical studies using CM formulas.
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Alérgenos/inmunología , Citocinas/metabolismo , Fórmulas Infantiles/efectos adversos , Leche/inmunología , Linfocitos T/inmunología , Linfocitos T/metabolismo , Animales , Especificidad de Anticuerpos/inmunología , Biomarcadores , Femenino , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Lactante , Mediadores de Inflamación/metabolismo , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Activación de Linfocitos , MasculinoRESUMEN
Recent studies in transgenic mice have revealed that expression of a dominant negative form of the transcription factor GATA-3 in T cells can prevent T helper cell type 2 (Th2)-mediated allergic airway inflammation in mice. However, it remains unclear whether GATA-3 plays a role in the effector phase of allergic airway inflammation and whether antagonizing the expression and/or function of GATA-3 can be used for the therapy of allergic airway inflammation and hyperresponsiveness. Here, we analyzed the effects of locally antagonizing GATA-3 function in a murine model of asthma. We could suppress GATA-3 expression in interleukin (IL)-4-producing T cells in vitro and in vivo by an antisense phosphorothioate oligonucleotide overlapping the translation start site of GATA-3, whereas nonsense control oligonucleotides were virtually inactive. In a murine model of asthma associated with allergic pulmonary inflammation and hyperresponsiveness in ovalbumin (OVA)-sensitized mice, local intranasal administration of fluorescein isothiocyanate-labeled GATA-3 antisense oligonucleotides led to DNA uptake in lung cells associated with a reduction of intracellular GATA-3 expression. Such intrapulmonary blockade of GATA-3 expression caused an abrogation of signs of lung inflammation including infiltration of eosinophils and Th2 cytokine production. Furthermore, treatment with antisense but not nonsense oligonucleotides induced a significant reduction of airway hyperresponsiveness in OVA-sensitized mice to levels comparable to saline-treated control mice, as assessed by both enhanced pause (PenH) responses and pulmonary resistance determined by body plethysmography. These data indicate a critical role for GATA-3 in the effector phase of a murine asthma model and suggest that local delivery of GATA-3 antisense oligonucleotides may be a novel approach for the treatment of airway hyperresponsiveness such as in asthma. This approach has the potential advantage of suppressing the expression of various proinflammatory Th2 cytokines simultaneously rather than suppressing the activity of a single cytokine.
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Asma/tratamiento farmacológico , Hiperreactividad Bronquial/tratamiento farmacológico , Proteínas de Unión al ADN/antagonistas & inhibidores , Oligonucleótidos Antisentido/uso terapéutico , Transactivadores/antagonistas & inhibidores , Animales , Eosinófilos/fisiología , Femenino , Factor de Transcripción GATA3 , Interleucina-4/biosíntesis , Interleucina-9/biosíntesis , Pulmón/patología , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/inmunología , Células Th2/metabolismoRESUMEN
BACKGROUND: Cow's milk is one of the most common causes of food allergy affecting approximately 2.5% of infants in the first years of their life. However, only limited information regarding the allergenic activity of individual cow's milk allergens is available. OBJECTIVE: To analyse the frequency of IgE reactivity and to determine the allergenic activity of individual cow's milk allergens. METHODS: A nitrocellulose-based microarray, based on purified natural and recombinant cow's milk allergens was used to determine IgE reactivity profiles using sera from 78 cow's milk-sensitized individuals of varying ages. The allergenic activity of the individual allergens was tested using patients' sera for loading rat basophil leukaemia cells (RBL) expressing the α-chain of the human receptor FcεRI. RESULTS: Using the microarray and the RBL assay, cow's milk allergens were assessed for frequency of IgE recognition and allergenic activity. Moreover, the RBL assay allowed distinguishing individuals without or with mild clinical reactions from those with severe systemic or gastrointestinal symptoms as well as persons who grew out cow's milk allergy from those who did not. CONCLUSIONS: Component-resolved testing using milk allergen microarrays and RBL assays seems to provide useful additional diagnostic information and may represent a basis for future forms of prophylactic and therapeutic strategies for cow's milk allergy.
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Alérgenos/inmunología , Inmunoglobulina E/inmunología , Hipersensibilidad a la Leche/diagnóstico , Hipersensibilidad a la Leche/inmunología , Proteínas de la Leche/inmunología , Adolescente , Adulto , Anciano , Animales , Antígenos CD/inmunología , Línea Celular Tumoral , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Análisis por Matrices de Proteínas , Ratas , Receptores Fc/inmunología , Adulto JovenRESUMEN
The frequency and severity of atopic disorders are steadily increasing, particularly in developing countries. The reason for this observation is not clear. Recent studies indicate that infections with viruses and especially with bacteria early in life may help to inhibit allergic Th2 responses by skewing the immune system towards Th1 responses. However, infections can also lead to the exacerbation of atopic disorders.
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Infecciones Bacterianas/inmunología , Hipersensibilidad Inmediata/inmunología , Virosis/inmunología , Animales , Antígenos Bacterianos/inmunología , Humanos , Hipersensibilidad/inmunología , Hipersensibilidad/fisiopatología , Hipersensibilidad Inmediata/microbiología , Hipersensibilidad Inmediata/fisiopatología , Hipersensibilidad Inmediata/virología , Lipopolisacáridos/inmunología , Infecciones Estafilocócicas/inmunología , Staphylococcus aureus/inmunología , Superantígenos/inmunologíaRESUMEN
Allergic sensitization and the development of effector functions are controlled by IL-4-secreting and IL-5-secreting type 2 T cells. Recent studies have provided new insights into the events triggering the development of type 1 and type 2 T cells, the discrimination of type 1 and type 2 effector T cells from various T-cell subsets, and the improvement of established and new therapeutic strategies, which are aimed at modulating such T-cell functions in the allergic patient.
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Citocinas/biosíntesis , Hipersensibilidad Inmediata/inmunología , Células Th2/metabolismo , Adyuvantes Inmunológicos/farmacología , Alérgenos/inmunología , Antiinflamatorios/farmacología , Citocinas/inmunología , Citocinas/metabolismo , Humanos , Hipersensibilidad Inmediata/terapia , Inmunoglobulina E/biosíntesis , Inmunoglobulina E/inmunología , Interleucina-10/inmunología , Interleucina-10/metabolismo , Interleucina-4/biosíntesis , Interleucina-4/inmunología , Interleucina-4/metabolismo , Modelos Inmunológicos , Esteroides , Subgrupos de Linfocitos T/inmunología , Células Th2/inmunologíaRESUMEN
Chronic skin colonization with Staphylococcus aureus is a well-known feature in atopic dermatitis. The aim of this study was to develop a human-SCID mouse model to analyze the possible role of bacterial superantigens in human allergic immune responses under in vivo conditions. SCID mice were reconstituted with peripheral blood mononuclear cells (between 2 and 9 x 10(7) cells per mouse) from atopic dermatitis patients sensitized to house dust mite allergen (Der p). Total and Der p specific antibody production required the following conditions: (i) injection of Der p; (ii) presence of CD14+ antigen-presenting cells; and (iii) IL-4 as shown by the inhibitory effect of human soluble IL-4 receptor on immunoglobulin E production. This model was used to study the immunomodulatory effects of the superantigen staphylococcal enterotoxin B in comparison with Der p. In intraperitoneally reconstituted human-SCID mice, topical treatment was ineffective in inducing skin inflammation. Therefore, additionally to intraperitoneal transfer, peripheral blood mononuclear cells from atopic donors were also injected intradermally. Such reconstituted SCID mice were then exposed via the skin to either Der p, staphylococcal enterotoxin B, or a combination of both. Maximal effects on epidermal inflammation and dermal T cell infiltration were obtained with staphylococcal enterotoxin B and Der p. Staphylococcal enterotoxin B alone was less effective and Der p only stimulated dermal T cell infiltration. These findings support the hypothesis that bacterial superantigens can act as trigger factors in allergic skin inflammation.
Asunto(s)
Antígenos Bacterianos/inmunología , Dermatitis Atópica/inmunología , Dermatitis Atópica/metabolismo , Hipersensibilidad/inmunología , Inmunoglobulina E/biosíntesis , Superantígenos/inmunología , Administración Tópica , Animales , Formación de Anticuerpos , Antígenos Dermatofagoides , Linfocitos B/fisiología , Senescencia Celular/fisiología , Dermatitis Atópica/sangre , Modelos Animales de Enfermedad , Enterotoxinas/inmunología , Enterotoxinas/farmacología , Glicoproteínas/inmunología , Humanos , Inmunoglobulina E/efectos de los fármacos , Inyecciones Intraperitoneales , Interleucina-4/fisiología , Ratones , Ratones SCID , Monocitos/trasplanteRESUMEN
BACKGROUND: Elevated expression of matrix metalloproteinases (MMPs) is suggested to have tumor marker potential in various tumors. MMPs are capable of disintegrating the basement membrane, which is a main characteristic of tumor invasion. They are specifically inactivated by tissue inhibitors of metalloproteinases (TIMPs). Squamous cell carcinomas of the head and neck (SCCHN) are known to be highly invasive tumors with early locoregional metastatic spread. PATIENTS AND METHODS: To investigate the tumor marker potential of MMPs in SCCHN, MMP-2, -3, -8, -9, -13 and TIMP-1 serum levels were determined in 73 patients and compared to 74 controls. A correlation with T- and N-status, UICC-staging and grading was performed. Additionally, the influence of inflammation on the MMP serum concentration was examined. RESULTS: Significant differences between patients with SCCHN and controls were seen for MMP-3, -8 and -9. A significant correlation was found between MMP-8 concentration and T-status, N-status and UICC-staging. No correlation with the grading of the tumor was observed. Inflammatory diseases did not affect MMP and TIMP levels significantly. CONCLUSION: Some MMPs are elevated in the serum of patients with SCCHN and especially MMP-8 showed interesting tumor marker potential.
Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma de Células Escamosas/diagnóstico , Neoplasias de Cabeza y Cuello/diagnóstico , Metaloproteinasas de la Matriz/sangre , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/enzimología , Neoplasias de Cabeza y Cuello/sangre , Neoplasias de Cabeza y Cuello/enzimología , Humanos , Metaloproteinasa 2 de la Matriz/sangre , Metaloproteinasa 3 de la Matriz/sangre , Metaloproteinasa 8 de la Matriz/sangre , Metaloproteinasa 9 de la Matriz/sangre , Valores de Referencia , Inhibidor Tisular de Metaloproteinasa-1/sangreRESUMEN
Serum matrix metalloproteinases (MMPs) and the macrophage colony-stimulating factor (M-CSF) are of potential interest as serum tumor markers in various malignancies. There is still a lack of reliable tumor markers in patients with squamous cell carcinoma of the head and neck (SCCHN). Therefore, the tumor marker potential of MMPs and M-CSF was investigated in these malignancies. Serum of 59 patients suffering from SCCHN and of 59 healthy volunteers was obtained. The concentration of MMP-3, MMP-8, MMP-9, and M-CSF was determined by sandwich enzyme immunoassays. The MMP- 3, -8, -9, as well as the M-CSF serum concentrations were significantly elevated in the patient group, compared to the healthy controls (p<0.001, p<0.05, p<0.001, p=0.002). There was significant correlation between the M-CSF and the MMP-3 serum concentration (p<0.0001), and between the M-CSF and the MMP-8 serum concentration (p=0.005). A significant correlation with the tumor stage was found only for MMP-8. MMP and M-CSF serum concentrations are of potential interest as serum tumor markers in SCCHN.
Asunto(s)
Carcinoma de Células Escamosas/sangre , Neoplasias de Cabeza y Cuello/sangre , Factor Estimulante de Colonias de Macrófagos/sangre , Metaloproteinasas de la Matriz/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Carcinoma de Células Escamosas/enzimología , Femenino , Neoplasias de Cabeza y Cuello/enzimología , Humanos , Técnicas para Inmunoenzimas , Masculino , Metaloproteinasa 3 de la Matriz/sangre , Metaloproteinasa 8 de la Matriz/sangre , Metaloproteinasa 9 de la Matriz/sangre , Persona de Mediana Edad , Valores de Referencia , Análisis de RegresiónRESUMEN
The development of allergic sensitization and inflammation is dependent on activation and stimulation of T cells that exhibit pro-allergic functions. A mouse model system was developed to study the role of T cells in allergic sensitization in more detail. Local sensitization of mice stimulates an allergen specific IgE/IgG1 response that is associated with the development of immediate type skin test responses and increased airway responsiveness (AR). Strains of mice are identified that are high or low responder animals for allergens including ovalbumin and house dust mite. Each allergen stimulates a different pattern of T-cell receptor V beta expressing T cells in local draining lymph nodes. To induce a state of increased AR, at least two separate events are required. The first event is the presence of allergen specific IgE/IgG1. The second event is characterized as a local allergen challenge at the site of the response. These T cells play a critical role in the regulation of the allergic immune response including IgE production and increased AR. Based on these results intervention strategies can be developed which specifically target the development and function of these allergen specific T-cell populations and modify their pro-allergic activities.
Asunto(s)
Hipersensibilidad Inmediata/inmunología , Modelos Inmunológicos , Linfocitos T/inmunología , Alérgenos/inmunología , Animales , Humanos , Inmunización , Inflamación/inmunología , Ratones , Receptores de Antígenos de Linfocitos T alfa-beta/inmunologíaRESUMEN
BACKGROUND: Clinical studies indicate that maternal exposure to probiotic bacteria may protect from the development of allergic disease later in life. OBJECTIVE: The purpose of this study was to analyse the effects of a perinatal Lactobacillus rhamnosus GG (LGG) supplementation on the development of allergic disorders in offspring. METHODS: Female BALB/c mice received intragastric LGG every other day before conception, during pregnancy and lactation (perinatal supplementation group) or before conception and during pregnancy only (prenatal supplementation group). Cytokine expression of placental tissues was examined. Offspring of LGG-supplemented and sham-exposed mothers were sensitized to Ovalbumin (OVA), followed by aerosol allergen challenges. Development of experimental asthma was assessed by bronchoalveolar lavage analysis, lung histology and lung function measurement. Cytokine production of splenic mononuclear cells was analysed following in vitro stimulation. RESULTS: Intestinal colonization with LGG was observed in mother mice only, but not in the offspring. However, a reduced expression of TNF-alpha, IFN-gamma, IL-5 as well as IL-10 was observed in mice derived from perinatally LGG-supplemented mothers, whereas IL-13 and IL-4 expression remained unchanged. Moreover, in offspring of prenatally or perinatally LGG-supplemented mothers allergic airway and peribronchial inflammation as well as goblet cell hyperplasia were significantly reduced as compared with mice derived from non-supplemented mothers. In contrast, airway hyperresponsiveness to methacholine was not affected. Exposure to LGG during pregnancy only shifted the placental cytokine expression pattern with a markedly increased TNF-alpha level. CONCLUSION: Our data suggest that LGG may exert beneficial effects on the development of experimental allergic asthma, when applied in a very early phase of life. Immunological effects are, at least in parts, mediated via the placenta, probably by induction of pro-inflammatory cell signals.
Asunto(s)
Alérgenos/inmunología , Animales Recién Nacidos/inmunología , Hipersensibilidad/inmunología , Lacticaseibacillus rhamnosus/inmunología , Efectos Tardíos de la Exposición Prenatal/inmunología , Probióticos/uso terapéutico , Animales , Femenino , Hipersensibilidad/prevención & control , Intercambio Materno-Fetal , Ratones , Ratones Endogámicos BALB C , Modelos Animales , EmbarazoRESUMEN
BACKGROUND: Epidemiological evidence underlines the impact of prenatal environmental factors on the development of postnatal allergies. In this regard an inverse correlation between lipopolysaccharide (LPS) exposure and development of childhood allergy has been found. OBJECTIVE: To assess the impact of prenatal LPS exposure on the development of postnatal respiratory allergies in a mouse model of experimental asthma. METHODS: Female BALB/c mice were exposed to LPS before conception and during pregnancy. Several weeks after birth offspring were sensitized to ovalbumin (OVA) followed by aerosol allergen challenges. RESULTS: Prenatal, maternal LPS-exposure enhanced neonatal IFN-gamma, but not IL-4 and IL-2 production. OVA sensitization of prenatally LPS-exposed mice was accompanied by a marked suppression in anti-OVA IgG1 and IgE as well as unchanged IgG2a antibody responses, paralleled by a significant reduction in IL-5 and IL-13 levels following mitogenic stimulation of splenic leucocytes. Assessment of bronchoalveolar lavage fluids following allergen challenges revealed a marked reduction in eosinophils and macrophages in these mice. Surprisingly, development of airway hyper-responsiveness, a hallmark of bronchial asthma, was not affected. CONCLUSION: This study provides first experimental evidence that LPS may already operate in prenatal life in order to modulate the development of allergies in the offspring.
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Asma/inmunología , Factores Inmunológicos/farmacología , Lipopolisacáridos/farmacología , Intercambio Materno-Fetal , Efectos Tardíos de la Exposición Prenatal , Animales , Animales Recién Nacidos , Anticuerpos Monoclonales/sangre , Líquido del Lavado Bronquioalveolar/inmunología , Broncoconstrictores , Exposición a Riesgos Ambientales , Femenino , Inmunoglobulina G/sangre , Factores Inmunológicos/inmunología , Inyecciones Intraperitoneales , Interferón gamma/inmunología , Lipopolisacáridos/inmunología , Cloruro de Metacolina , Ratones , Ratones Endogámicos BALB C , Modelos Animales , Ovalbúmina , EmbarazoRESUMEN
BACKGROUND AND AIM: Atopic dermatitis (AD) is a common chronic inflammatory skin disease often accompanied by cutaneous Staphylococcus aureus colonization and, in this regard, especially complicated by the presence of superantigen-producing strains. Because IgG antibodies comprise an important defence mechanism of the adaptive immune system against bacteria, it was investigated whether AD patients have an abnormal pattern or distribution of superantigen-specific IgG subclass antibodies in association with disease severity and activity. METHODS: Staphylococcal enterotoxin B (SEB) and staphylococcal enterotoxin C1 (SEC1) specific IgG antibody subclasses were assessed in n=89 adult AD patients with mild to severe disease activity as determined by the SCORAD score and in n=28 healthy age-matched controls. Results were correlated with the current status of bacterial skin colonization and severity score. RESULTS: Thirty-eight per cent of the AD patients showed a selective deficiency in IgG2 antibodies against SEC1 compared with only 14% in the control group. The absence of these antibodies was found in both currently colonized and non-colonized AD patients and was associated with a severe phenotype (SCORAD more than 40 points in two-thirds of the deficient patients). However, these patients had normal production levels of IgG2 antibodies against pneumococcal capsular polysaccharide (PCP) and SEB, but higher IgG1 and IgG4 titres against SEC1. Except for elevated total IgG1, total IgG subclass levels were normal in this AD subgroup. Yet, peripheral blood mononuclear cells (PBMCs) derived from these patients clearly produced IL-4 and IL-5 upon SEC1 re-stimulation whereas PBMCs from those providing SEC1-specific IgG2 antibodies failed in the production of these cytokines. CONCLUSION: A subgroup of AD patients suffers from a selective deficiency to produce anti-SEC1 IgG2 antibodies. This patient group is characterized by a severe AD phenotype.
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Anticuerpos Antiidiotipos/sangre , Dermatitis Atópica/inmunología , Enterotoxinas/inmunología , Inmunoglobulina G/inmunología , Superantígenos/inmunología , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Células Cultivadas , Citocinas/análisis , Femenino , Humanos , Leucocitos Mononucleares/inmunología , Masculino , Persona de Mediana Edad , Polisacáridos Bacterianos/inmunología , Estadísticas no Paramétricas , Células Th2/inmunologíaRESUMEN
In recent decades, the prevalence of allergic diseases including bronchial asthma, hay fever and atopic dermatitis, has risen steadily in high-income countries. The underlying mechanisms for this phenomenon remain largely unknown. Since the natural mutation rate is low, altered environmental and lifestyle conditions are thought to play an important role. Epidemiological and clinical studies have provided indirect evidence that infections may prevent the development of atopy and atopic disease. This is referred to as the "hygiene hypothesis". According to the hygiene hypothesis, viral and/or bacterial infections could inhibit the T-helper (Th)-2 immune response associated with atopic reactions by stimulating a Th-1 response involved in defence of bacterial infections and delayed-type hypersensitivity reactions. In particular, the prenatal period and early childhood are considered to be critical for the establishment and maintenance of a normal Th-1/Th-2 balance. On the other hand, several studies suggested that infections exacerbate established allergic diseases, e.g. bronchial asthma, airway hyperresponsiveness and atopic dermatitis. Therefore, viral and/or microbial infections and/or their products may have bidirectional effects on the development of allergy and asthma. This review will focus on recent findings related to the interaction between allergic disorders and infectious diseases, with the main emphasis on bacterial infections.
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Antígenos Bacterianos/inmunología , Asma/inmunología , Hipersensibilidad/inmunología , Animales , Vacuna BCG/inmunología , ADN Bacteriano/inmunología , Humanos , Recién Nacido , Infecciones/inmunología , Lipopolisacáridos/inmunología , Infecciones por Mycobacterium/inmunología , Superantígenos/inmunología , Linfocitos T Colaboradores-Inductores/inmunologíaRESUMEN
Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease. Influx of activated T cells into the skin lesions represents a hallmark in AD. Recent results indicate a dynamic T-cell-derived cytokine production in AD. In addition to the well-known TH-2 component, chronic lesions and late-phase allergic responses are characterized by an TH-1/TH-0 cytokine pattern. Although there is no doubt that aeroallergens can contribute to the elicitation of acute- and late-phase allergic responses in AD, their role in the immunopathogenesis is controversally discussed. Recent attention has been given to the long-known phenomenon of persistent colonization of AD skin with S. aureus and the potential role of S. aureus-derived superantigens. Evidence from several in vitro and in vivo studies suggests that such bacterial superantigens have the potency to trigger chronic T-cell-mediated skin inflammation. Although these data are certainly suggestive, further clinical studies are required to elucidate the role of bacterial superantigens in initiation, maintenance and, especially, chronicity of skin inflammation.
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Citocinas/inmunología , Citocinas/metabolismo , Dermatitis Atópica/inmunología , Superantígenos/inmunología , Linfocitos T/inmunología , Linfocitos T/fisiología , Pared Celular/inmunología , Pared Celular/metabolismo , Humanos , Inflamación/inmunología , Inflamación/metabolismo , Interferón gamma/inmunología , Interferón gamma/metabolismo , Interleucina-4/inmunología , Interleucina-4/metabolismo , Interleucina-5/inmunología , Interleucina-5/metabolismo , Staphylococcus aureus/inmunología , Linfocitos T/metabolismoRESUMEN
Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation of the airways, development of emphysema and irreversible airway obstruction. Macrophages, neutrophils and CD8+ T cells and their products have been shown to play an important role in the initiation and maintenance of these processes. In contrast, the mechanisms underlying COPD pathogenesis still remain uncertain. This article focuses on the generation of an animal model that mirrors some features of human COPD in association with a progredient airflow limitation.
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Bronquitis Crónica/inducido químicamente , Modelos Animales de Enfermedad , Dióxido de Nitrógeno/toxicidad , Enfermedad Pulmonar Obstructiva Crónica/inducido químicamente , Animales , Bronquitis Crónica/complicaciones , Bronquitis Crónica/patología , Exposición por Inhalación , Ratones , Ratones Endogámicos C57BL , Enfermedad Pulmonar Obstructiva Crónica/etiología , Enfermedad Pulmonar Obstructiva Crónica/patologíaRESUMEN
From a systemic point of view, Staabs' test findings are always a diagnostic construction. Criteria for their utility in a certain context is whether in addition to other information sources, it can give meaningful indications for the diagnosis and treatment (comp. for instance, also Priebe's 1989 thoughts on psychiatric diagnosis). Nevertheless or just for that reason is the consideration of relatively constant characteristics of a material, the test person as well as relative observation and description dimensions indispensable in order to prevent the danger of options and "overinterpretation". In this paper, an attempt was made at combining the characteristics that have been crystallized as relevant in the work with Staabs' test over the decades up till now and to put them into a theoretic (systemic) diagnostic context. Under these presuppositions, the Staabs' test presents a particularly suitable procedure for making contact with as well as for the diagnosis and treatment, above all, of children and adolescents. Also the use of relationship and family diagnostics and treatment is possible. At the same time Staabs' test has the inestimable advantage in that the test person's cooperation is only very rarely unattainable; in other procedures this is more often the case.
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Desarrollo de la Personalidad , Técnicas Proyectivas , Teoría Psicoanalítica , Terapia Psicoanalítica , Adolescente , Niño , Trastornos de la Conducta Infantil/psicología , Preescolar , Femenino , Humanos , Masculino , Desarrollo PsicosexualRESUMEN
BACKGROUND: In patients with allergic bronchial asthma, a strong relationship between elevated serum IgE antibody titres and the development of increased airway responsiveness (AR) has been demonstrated. To further elucidate the relationship between human (hu) IgE and development of increased AR, we developed an in vivo model utilizing immuno-compromised severe combined immuno-deficiency (SCID) mice. METHODS: SCID mice were either reconstituted with peripheral blood mononuclear cells (PBMC) from non-atopic, healthy or atopic individuals sensitized against house dust mite allergen (Der p), or passively sensitized with plasma from non-atopic, healthy or atopic individuals. RESULTS: In both systems, atopic hu-SCID mice developed increased AR. The following results suggest that these responses were mediated via IgE antibodies: increased AR did not occur after transfer of either PBMC or IgE-negative plasma from non-atopic individuals; increased AR occurred simultaneous with increased serotonin release detected 15 min after allergen-aerosol challenge in bronchoalveolar lavage fluid; and increased AR required at least two allergen-aerosol challenges. SCID mice reconstituted with serum containing anti-Der p IgE antibodies developed positive immediate-type skin test responses to intradermal injection of Der p as well as anti-hu-IgE antibody. In addition, IgE binding to skin mast cells was demonstrated by immunohistochemistry. Furthermore, intravenous challenge of hu anti-Der p positive SCID mice with Der p resulted in systemic anaphylaxis. CONCLUSION: These data provide evidence that passive immunization of SCID mice with hu IgE alters AR and that T cells and eosinophils were not a requirement for the development of increased AR in this model.
Asunto(s)
Hiperreactividad Bronquial , Hipersensibilidad Inmediata/inmunología , Inmunización Pasiva , Inmunoglobulina E/administración & dosificación , Piel/inmunología , Animales , Anticuerpos Antiidiotipos/inmunología , Antígenos Dermatofagoides/inmunología , Proteínas de Artrópodos , Asma/inmunología , Cisteína Endopeptidasas , Humanos , Inmunoglobulina G/inmunología , Ratones , Ratones SCID , Modelos Animales , Pruebas CutáneasRESUMEN
The effects of repeated ozone exposures on the development of immune responses toward ovalbumin (OVA) were investigated in BALB/c and C57BL/6 mice. Ozone exposures (180 to 500 microg/m(3); 4 h, three times/wk for 4 wk) were combined with a protocol of OVA-aerosol exposure (1% OVA). Immediate cutaneous hypersensitivity (ICHS) reactions and antibody titers were assessed in parallel to cytokine levels of bronchoalveolar lavage fluids. In BALB/c mice, ozone triggered a T-helper (Th)2-like response indicated by dose-dependent increases in total serum immunoglobulin (Ig) E (from 133 to 821 ng/ml), interleukin (IL)-4 (from 60 to 208 pg/ml), and IL-5 levels (from 43 to 356 pg/ml), and by the recruitment of eosinophils and lymphocytes into the airways. Ozone exposure (500 microg/m(3)) in parallel to OVA-aerosol exposure increased anti-OVA IgG(1) antibody titers by 80%, leukotrienes (C(4)/D(4)/E(4)) by 60%, and airway responsiveness (11.3 versus 7.2 mg/ml methacholine), and doubled the frequency of positive ICHS reactions. In C57BL/6 mice, only the combination of OVA and ozone exposure induced positive ICHS reactions, doubled anti-OVA IgG(1), and suppressed anti-OVA IgG(2a) (-64%) antibody titers. Ozone, therefore, shifted the immune responses to OVA toward a Th2-like pattern in both "IgE-high responder" (BALB/c) and "IgE-low responder" (C57BL/6) mice.
Asunto(s)
Hipersensibilidad Inmediata/inmunología , Oxidantes Fotoquímicos/farmacología , Ozono/farmacología , Administración por Inhalación , Animales , Hiperreactividad Bronquial/inmunología , Líquido del Lavado Bronquioalveolar/citología , Recuento de Células/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Inmunoglobulina E/sangre , Inmunoglobulina E/efectos de los fármacos , Inmunoglobulina G/sangre , Inmunoglobulina G/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ovalbúmina/inmunología , Ovalbúmina/farmacología , Células Th2/citología , Células Th2/efectos de los fármacos , Células Th2/inmunologíaRESUMEN
INTRODUCTION: The purpose of this study was to prove the effect of wear particles, especially Tivanium, in the mechanism of the aseptic loosening of total joint prostheses. MATERIALS AND METHODS: Therefore, human bone marrow cell cultures were incubated with titanium-aluminium-vanadium particles of different concentrations which were added after the seventh day of culture (10(9), 10(8), 10(7), 10(6) particles per ml medium). From this time starts the real culture period (2 weeks). During these two weeks the medium was changed and the supernatants were sampled. Using an ELISA the cytokine levels of interleukin-6, interleukin-1beta, TNF-alpha and LDH were measured approximately every second day (1, 3, 6, 8, 10, 14). As a marker for toxicity the activity of LDH was determined. RESULTS: Incubation of a human bone marrow cell culture with titanium-aluminium-vanadium particles led to a maximum release of interleukin-6, interleukin-1beta, and TNF-alpha at high particle concentration (10(9) particles per ml medium). An increase of interleukin-1beta was only detectable at particle concentrations of 10(9) per ml medium. Exposure of the human bone marrow cell culture to titanium-aluminium-vanadium particles was toxic for high particle concentrations (10(9) particles per ml medium), as reflected by release of the intracellular enzyme LDH. DISCUSSION: This study shows the ability of tivanium wear particles in a human bone marrow cell culture to induce a signfically higher release of proinflammatory and osteolytic mediators which are responsible for the aseptic loosening of prosthesis and the problem of revisions. In comparison to other cell studies, our results were explained by the human bone marrow cell culture. The human bone marrow is the real effector tissue source "in situ" because the prosthesis is localised intramedullarly.