RESUMO
Nailfold capillaroscopy has become an established method in adults for the evaluation of structural abnormalities of the microcirculation associated with rheumatic disease. It is a cornerstone for the diagnostic work-up of patients with Raynaud's phenomenon and the early diagnosis of systemic sclerosis. However, this non-invasive examination may also be valuable in children and adolescents with rheumatic diseases. Based on the scarce data available, this review focuses on capillaroscopic findings in healthy children and adolescents as well as in children with juvenile systemic sclerosis, juvenile dermatomyositis, juvenile idiopathic arthritis, and Raynaud's phenomenon. In addition, it outlines the potential benefits and limitations of nailfold capillaroscopy for routine care in paediatric rheumatology.
Assuntos
Dermatomiosite/diagnóstico , Dedos/irrigação sanguínea , Angioscopia Microscópica/métodos , Microvasos , Doença de Raynaud/diagnóstico , Escleroderma Sistêmico/diagnóstico , Adolescente , Doenças Autoimunes/diagnóstico , Criança , Humanos , Microcirculação , Doenças Reumáticas/diagnósticoRESUMO
OBJECTIVE: To evaluate the genetic findings, demographic features and clinical presentation of tumour necrosis factor receptor-associated autoinflammatory syndrome (TRAPS) in patients from the Eurofever/EUROTRAPS international registry. METHODS: A web-based registry collected retrospective data on patients with TNFRSF1A sequence variants and inflammatory symptoms. Participating hospitals included paediatric rheumatology centres and adult centres with a specific interest in autoinflammatory diseases. Cases were independently validated by experts in the disease. RESULTS: Complete information on 158 validated patients was available. The most common TNFRSF1A variant was R92Q (34% of cases), followed by T50M (10%). Cysteine residues were disrupted in 27% of cases, accounting for 39% of sequence variants. A family history was present in 19% of patients with R92Q and 64% of those with other variants. The median age at which symptoms began was 4.3 years but 9.1% of patients presented after 30 years of age. Attacks were recurrent in 88% and the commonest features associated with the pathogenic variants were fever (88%), limb pain (85%), abdominal pain (74%), rash (63%) and eye manifestations (45%). Disease associated with R92Q presented slightly later at a median of 5.7 years with significantly less rash or eye signs and more headaches. Children were more likely than adults to present with lymphadenopathy, periorbital oedema and abdominal pains. AA amyloidosis has developed in 16 (10%) patients at a median age of 43 years. CONCLUSIONS: In this, the largest reported case series to date, the genetic heterogeneity of TRAPS is accompanied by a variable phenotype at presentation. Patients had a median 70 symptomatic days a year, with fever, limb and abdominal pain and rash the commonest symptoms. Overall, there is little evidence of a significant effect of age or genotype on disease features at presentation.
Assuntos
Doenças Hereditárias Autoinflamatórias/genética , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos de Coortes , Progressão da Doença , Exantema/etiologia , Feminino , Febre/etiologia , Genótipo , Doenças Hereditárias Autoinflamatórias/complicações , Doenças Hereditárias Autoinflamatórias/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Fenótipo , Sistema de Registros , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: The scheduled update to the German S3 guidelines on fibromyalgia syndrome (FMS) by the Association of the Scientific Medical Societies ("Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften", AWMF; registration number 041/004) was planned starting in March 2011. MATERIALS AND METHODS: The development of the guidelines was coordinated by the German Interdisciplinary Association for Pain Therapy ("Deutsche Interdisziplinären Vereinigung für Schmerztherapie", DIVS), 9 scientific medical societies and 2 patient self-help organizations. Eight working groups with a total of 50 members were evenly balanced in terms of gender, medical field, potential conflicts of interest and hierarchical position in the medical and scientific fields. Literature searches were performed using the Medline, PsycInfo, Scopus and Cochrane Library databases (until December 2010). The grading of the strength of the evidence followed the scheme of the Oxford Centre for Evidence-Based Medicine. RESULTS: Current data do not identify distinct etiologic or pathophysiological factors mediating development of FMS. The development of FMS is associated with inflammatory rheumatic diseases (EL2b), with gene polymorphisms of the 5-hydroxytryptamine (HT)(2) receptor (EL3a), lifestyle factors (smoking, obesity, lack of physical activity; EL2b), physical and sexual abuse in childhood and adulthood (EL3a). CONCLUSION: FMS is most likely the result of various pathogenetic factors and pathophysiological mechanisms. The English full-text version of this article is available at SpringerLink (under "Supplemental").
Assuntos
Fibromialgia/etiologia , Fibromialgia/fisiopatologia , Adulto , Comportamento Cooperativo , Medicina Baseada em Evidências , Fibromialgia/psicologia , Alemanha , Humanos , Comunicação Interdisciplinar , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Transtornos Somatoformes/etiologia , Transtornos Somatoformes/fisiopatologia , Transtornos Somatoformes/psicologiaRESUMO
BACKGROUND: The scheduled update to the German S3 guidelines on fibromyalgia syndrome (FMS) by the Association of the Scientific Medical Societies ("Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften", AWMF; registration number 041/004) was planned starting in March 2011. MATERIALS AND METHODS: The development of the guidelines was coordinated by the German Interdisciplinary Association for Pain Therapy ("Deutsche Interdisziplinären Vereinigung für Schmerztherapie", DIVS), 9 scientific medical societies and 2 patient self-help organizations. Eight working groups with a total of 50 members were evenly balanced in terms of gender, medical field, potential conflicts of interest and hierarchical position in the medical and scientific fields. Literature searches were performed using the Medline, PsycInfo, Scopus and Cochrane Library databases (until December 2010). The grading of the strength of the evidence followed the scheme of the Oxford Centre for Evidence-Based Medicine. The formulation and grading of recommendations was accomplished using a multi-step, formal consensus process. The guidelines were reviewed by the boards of the participating scientific medical societies. RESULTS AND CONCLUSION: The diagnosis FMS in children and adolescents is not established. In so-called juvenile FMS (JFMS) multidimensional diagnostics with validated measures should be performed. Multimodal therapy is warranted. In the case of severe pain-related disability, therapy should be primarily performed on an inpatient basis. The English full-text version of this article is available at SpringerLink (under "Supplemental").
Assuntos
Dor Crônica/diagnóstico , Dor Crônica/reabilitação , Fibromialgia/diagnóstico , Fibromialgia/reabilitação , Atividades Cotidianas/classificação , Atividades Cotidianas/psicologia , Adolescente , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/psicologia , Transtornos de Ansiedade/reabilitação , Criança , Dor Crônica/psicologia , Terapia Combinada , Comorbidade , Comportamento Cooperativo , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/psicologia , Transtorno Depressivo/reabilitação , Medicina Baseada em Evidências , Fibromialgia/psicologia , Alemanha , Humanos , Comunicação Interdisciplinar , Admissão do Paciente , Equipe de Assistência ao Paciente , Qualidade de Vida/psicologia , Centros de ReabilitaçãoRESUMO
BACKGROUND: Immune-modulation such as tolerance induction appears to be an upcoming concept to prevent development of atopic diseases. Pregnancy might present a critical period for preventing allergic sensitization of the progeny. We investigated the effect of maternal allergen exposures during pregnancy on allergen-induced sensitization and airway inflammation in the offspring in a murine model. METHODS: BALB/c mice were exposed to aerosolized ovalbumin (OVA) three times per week from day 7 of pregnancy until delivery (day 0). Offspring were systemically sensitized by six intraperitoneal injections with OVA between postnatal days 21 and 35, prior to airway allergen challenges on days 48, 49, and 50. Analyses were performed on day 52. To examine long-lasting effects of maternal OVA exposures some offspring were sensitized between days 115 and 129; analyses took place on day 147. RESULTS: Compared to maternal placebo exposures, maternal OVA exposures suppressed OVA-specific IgE serum levels and inhibited development of allergen-induced airway inflammation in the OVA-sensitized offspring on both days 52 and 147. This protective effect was associated with a shift from a predominant Th2 immune response toward a predominant production of the cytokines IFN-γ and IL-10. Further, maternal OVA exposures were associated with development of CD25(+) Foxp3(+) regulatory T cells (T(regs)) in the OVA-sensitized offspring. Depletion of T(regs) or neutralization of IL-10 prior to allergen sensitization re-established OVA-induced sensitization and eosinophilic airway inflammation in the OVA-sensitized offspring. CONCLUSIONS: In our model, maternal allergen exposures during pregnancy prevented later allergen-mediated sensitization and airway inflammation by allergen-specific tolerance induction in the offspring.
Assuntos
Alérgenos/imunologia , Inflamação/prevenção & controle , Exposição Materna , Efeitos Tardios da Exposição Pré-Natal , Hipersensibilidade Respiratória/prevenção & controle , Aerossóis , Alérgenos/administração & dosagem , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Tolerância Imunológica , Imunomodulação , Inflamação/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/administração & dosagem , Ovalbumina/imunologia , Gravidez , Hipersensibilidade Respiratória/imunologiaAssuntos
Irritantes/toxicidade , Sistema Respiratório/efeitos dos fármacos , Sistema Respiratório/metabolismo , Canais de Potencial de Receptor Transitório/metabolismo , Aldeídos/farmacologia , Animais , Deleção de Genes , Regulação da Expressão Gênica , Peroxidação de Lipídeos , Camundongos , Neurônios Aferentes/fisiologia , Estresse Oxidativo , Canal de Cátion TRPA1 , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismo , Canais de Potencial de Receptor Transitório/genéticaRESUMO
OBJECTIVE: The aim was to develop a guideline for diagnostic procedures and treatment of juvenile fibromyalgia syndrome (JFMS) in cooperation with 10 German medical and psychological associations and 2 patient self-help groups. METHODS: A systematic literature search, including all controlled studies evaluating diagnosis and treatment of JFMS, was performed in the Cochran Collaboration Reviews (1993-12/2006), Medline (1980-12/2006), PsychInfo (1966-12/2006) and Scopus (1980-12/2006). Levels of evidence were assigned according to the classification system of the Oxford Centre for Evidence-Based Medicine. Grading of the strengths of recommendations was performed according to the German program for disease management guidelines. Standardized procedures to reach a consensus on recommendations were used. RESULTS: Pain in children/adolescents involving several body areas and lasting >3 months without an obvious somatic cause is called JFMS or pain amplification syndrome. Therapeutically, a multidisciplinary concept with psychotherapy and physiotherapy, relaxation techniques and patient education is recommended. CONCLUSION: These guideline will contribute to a better recognition and standardized care of patients with JFMS and facilitate clinical studies.
Assuntos
Fibromialgia/reabilitação , Adolescente , Criança , Terapia Combinada , Diagnóstico Diferencial , Medicina Baseada em Evidências , Fibromialgia/diagnóstico , Humanos , Equipe de Assistência ao Paciente , Grupos de Autoajuda , Sociedades MédicasRESUMO
OBJECTIVE: To write a systematic review on the etiology and pathophysiology of the fibromyalgia syndrome (FMS) and of chronic widespread pain (CWP). METHODS: An interdisciplinary level-3 guideline (i.e. systematic literature search and assessment, logic analysis, formal consensus procedure) for the diagnosis and therapy of FMS was created in cooperation with 10 medical and psychological societies and 2 patient self-help organizations. A literature search was performed covering all available review articles on the etiology and pathophysiology of FMS and CWP using the Cochrane Collaboration Reviews (1993-12/2006), Medline (1980-2006), PsychInfo (1966-12/2006), and Scopus (1980-12/2006). For the assignment of evidence classes the system of the Oxford Centre for Evidence-Based Medicine was applied. Consensus was achieved by a multi-step nominal group procedure. RESULTS: FMS aggregates in families (evidence level 2c). Physical and psychological stress at the workplace are risk factors for the development of CWP and FMS. Affective disorders are risk factors for the development and maintenance of FMS. Operant learning mechanisms and sensitization are risk factors for the chronification of FMS (evidence levels 2b). Several factors are associated with the pathophysiology of FMS, but the causal relationship is unclear. This includes alterations of central pain pathways, hyporeactivity of the hypothalamus-pituitary-adrenal axis, increased systemic pro-inflammatory and reduced anti-inflammatory cytokine profiles and disturbances in the dopaminergic and serotonergic systems. CONCLUSIONS: FMS is the common final product of various etiological factors and pathophysiological mechanisms.
Assuntos
Fibromialgia/etiologia , Sistema Nervoso Autônomo/fisiopatologia , Sistema Nervoso Central/fisiopatologia , Diagnóstico Diferencial , Medicina Baseada em Evidências , Fibromialgia/diagnóstico , Fibromialgia/fisiopatologia , Fibromialgia/psicologia , Predisposição Genética para Doença , Alemanha , Humanos , Equipe de Assistência ao Paciente , Fatores de Risco , Meio Social , Estresse PsicológicoRESUMO
BACKGROUND: Infection with influenza virus has been associated with seemingly opposing effects on the development of asthma. However, there are no data about the effects of mucosal vaccination with inactivated influenza on the inception of allergic asthma. OBJECTIVE: To assess the immunological effects of inhaled inactivated influenza vaccine, using two different types of flu vaccines, on the inception of allergic sensitization and allergen-mediated airway disease in a mouse model. METHODS: BALB/c mice were intranasally or intratracheally vaccinated with whole or split influenza virus vaccine (days -1 or -1, 27) before systemic sensitization with ovalbumin (OVA) (days 1, 14) and repeated airway allergen challenges (days 28-30). Allergen sensitization (IgE serum levels), airway inflammation (differential cells in bronchoalveolar lavage fluid) and airway hyper-reactivity (AHR) (in vivo lung function) were analysed. RESULTS: The intranasal instillation of whole influenza vaccine before allergen sensitization significantly reduced the serum levels of total and OVA-specific IgE as well as allergen-induced AHR. Prevention was due to an allergen-specific shift from a predominant T helper (Th)2- towards a Th1-immune response. Application of split influenza vaccine did not show the same preventive effect. CONCLUSION: Intranasal administration of inactivated whole influenza vaccine reduced subsequent allergen sensitization and prevented allergen-induced AHR. Our results show that the composition of the influenza vaccine has a major influence on subsequent development of allergen-induced sensitization and AHR, and suggest that mucosal inactivated whole influenza vaccination may represent a step towards the development of a preventive strategy for atopic asthma.
Assuntos
Asma/prevenção & controle , Hiper-Reatividade Brônquica/prevenção & controle , Vírus da Influenza A/imunologia , Vacinas contra Influenza/imunologia , Células Th1/imunologia , Células Th2/imunologia , Vacinas de Produtos Inativados/imunologia , Administração Intranasal , Alérgenos/imunologia , Alérgenos/toxicidade , Animais , Asma/induzido quimicamente , Asma/imunologia , Hiper-Reatividade Brônquica/induzido quimicamente , Hiper-Reatividade Brônquica/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Feminino , Vacinas contra Influenza/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Ovalbumina/toxicidade , Vacinas de Produtos Inativados/administração & dosagemRESUMO
BACKGROUND: Co-vaccination with cellular pertussis vaccine down-regulates allergic sensitization to diphtheria and tetanus antigens. Using a murine model, we investigated whether vaccination with diphtheria/tetanus toxoids, administered separately or simultaneously with the whole cell vaccine of Bordetella pertussis, inhibits subsequent allergen-induced immune and inflammatory responses. METHODS: BALB/c-mice were vaccinated intracutaneously with a combination of diphtheria and tetanus toxoids or a combination of diphtheria and tetanus toxoids with a whole cell vaccine of B. pertussis (three times, days -21 to -7) prior to systemic sensitization (days 1-14) and repeated airway challenges (days 28-30) with ovalbumin. RESULTS: Compared with negative controls, systemic sensitization and airway allergen challenges induced high serum levels of allergen-specific IgE, predominant Th2-type cytokine production, airway inflammation and development of in vivo airway hyperreactivity. Vaccination with diphtheria and tetanus toxoids prior to sensitization suppressed IgE formation and development of eosinophilic airway inflammation. Co-vaccination with a whole cell pertussis vaccine inhibited allergen sensitization, airway inflammation and development of in vivo airway hyperreactivity. Prevention was due to an allergen-specific and general shift from a predominant Th2 towards a predominant Th1 immune response. CONCLUSION: Vaccination with diphtheria and tetanus toxoids alone or in combination with whole cell pertussis vaccine prior to allergen sensitization prevented allergen-induced Th2 immune responses. Vaccine antigens may down-regulate allergic responses to a range of common allergens.
Assuntos
Asma/prevenção & controle , Hiper-Reatividade Brônquica/prevenção & controle , Vacina contra Difteria e Tétano/uso terapêutico , Vacina contra Difteria, Tétano e Coqueluche/uso terapêutico , Alérgenos/imunologia , Animais , Asma/imunologia , Asma/fisiopatologia , Hiper-Reatividade Brônquica/imunologia , Líquido da Lavagem Broncoalveolar/citologia , Proliferação de Células , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Leucócitos Mononucleares/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Baço/citologia , Baço/imunologiaRESUMO
BACKGROUND: Interleukin-18 (IL-18) plays an important role in the regulation of TH1 as well as TH2 immunologic responses and thus in the development of chronic inflammatory diseases. Positive association studies of polymorphisms in IL-18 with different diseases have underlined the involvement of IL-18 in the pathogenetics processes. Our interest was to test polymorphisms of IL-18 for association with a typical TH1-mediated disease--juvenile idiopathic arthritis--and the TH2-mediated disease bronchial asthma in Caucasian children. METHODS: We genotyped five polymorphisms that were in association with chronic inflammatory diseases (-607C, -137C, 113G, 127T, and -133G). This was performed by restriction fragment length polymorphism in populations of asthmatic children, control individuals, and children with antinuclear antibodies (ANA)-positive juvenile idiopathic arthritis. Statistical analysis was performed by the Armitage trend test; haplotypes were calculated by the Arlequine program. RESULTS: No significant association was found between any single nucleotide polymorphism or any haplotype and bronchial asthma or ANA-positive juvenile idiopathic arthritis. CONCLUSION: We conclude that the effect of IL-18 in the immunologic context of diseases like bronchial asthma or juvenile arthritis might be too complex to be reflected in a simple one-way association study. Furthermore, the polymorphisms under investigation might be nonfunctional.
Assuntos
Artrite Juvenil/genética , Asma/genética , Interleucina-18/genética , Polimorfismo Genético , Adolescente , Artrite Juvenil/imunologia , Asma/imunologia , Criança , Pré-Escolar , Genótipo , Humanos , Células Th2/imunologiaRESUMO
BACKGROUND: Histamine-1-receptor (H1R)-antagonists were shown to influence various immunological functions on different cell types and may thus be employed for immune-modulating strategies for the prevention of primary immune responses. OBJECTIVE: The aim of this study was to investigate the effects of an H1R-antagonist on allergen-induced sensitization, airway inflammation (AI) and airway hyper-reactivity (AHR) in a murine model. METHODS: BALB/c mice were systemically sensitized with ovalbumin (OVA) (six times, days 1-14) and challenged with aerosolized allergen (days 28-30). One day prior to the first and 2 h prior to every following sensitization, mice received either 1 or 0.01 microg of desloratadine (DL) or placebo per os. RESULTS: Sensitization with OVA significantly increased specific and total IgE and IgG1 serum levels, as well as in vitro IL-5 and IL-4 production by spleen and peribronchial lymph node (PBLN) cells. Sensitized and challenged mice showed a marked eosinophilic infiltration in broncho-alveolar lavage fluids and lung tissues, and developed in vivo AHR to inhaled methacholine. Oral treatment with DL prior to OVA sensitization significantly decreased production of OVA-specific IgG1, as well as in vitro Th2-cytokine production by spleen and PBLN cells, compared with OVA-sensitized mice. Moreover, eosinophilic inflammation and development of in vivo AHR were significantly reduced in DL-treated mice, compared with sensitized controls. CONCLUSION: Treatment with H1R-anatagonist prior to and during sensitization suppressed allergen-induced Th2 responses, as well as development of eosinophilic AI and AHR. This underscores an important immune modulating function of histamine, and implies a potential role of H1R-anatagonists in preventive strategies against allergic diseases.
Assuntos
Alérgenos/farmacologia , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Hipersensibilidade/prevenção & controle , Loratadina/análogos & derivados , Loratadina/uso terapêutico , Administração Oral , Animais , Hiper-Reatividade Brônquica , Células Cultivadas , Feminino , Hipersensibilidade/imunologia , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Interleucina-4/imunologia , Interleucina-5/imunologia , Pulmão/imunologia , Linfonodos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Ovalbumina , Baço/imunologiaRESUMO
Exposure early in life to organic dusts containing immunomodulatory components such as endotoxins and immunizing components such as aeroallergens may greatly influence whether subsequent encounters with allergens lead rather to sensitization or unresponsiveness. We investigated the effects of endotoxin in the context of allergen-mediated immune responses in a murine model of allergen sensitization. Systemic sensitization with ovalbumin induced high serum levels of allergen-specific IgE, predominant Th2-type cytokine production, eosinophilic airway inflammation and in vivo airway hyperreactivity. Endotoxins were either applied systemically prior to sensitization, or via the airways prior to airway challenges, or by repeated inhalation during the first weeks of life prior to subsequent sensitization. Different effects of endotoxins on allergen-induced immune responses may be attributed to differences in dosing, route of application, time relationship with allergen sensitization and the concurrent exposure to endotoxin and allergen. The results of these studies may help to define the effects of endotoxin on allergen-mediated immune reactions and to further delineate the important interrelationships between environment and disease development. Finally, this may lead to new strategies in the prevention and treatment of allergic diseases.
Assuntos
Alérgenos/imunologia , Modelos Animais de Doenças , Hipersensibilidade Imediata/imunologia , Lipopolissacarídeos/administração & dosagem , Ovalbumina/administração & dosagem , Animais , Animais Recém-Nascidos , Formação de Anticorpos/efeitos dos fármacos , CamundongosRESUMO
BACKGROUND: The release of cytokines [interleukin-6 (IL-6), IL-8 and tumor necrosis factor-alpha (TNF-alpha)] by skin cells is involved in the pathogenesis of atopic dermatitis (AD). OBJECTIVE: To evaluate the effect of low-dose cyclosporin A (CyA) on clinical symptoms and cytokine secretion in severe pediatric AD. METHODS: Ten children with severe AD (SCORAD index >50) were treated for 8 weeks with CyA. The initial dose of 2.5 mg/kg/day was titrated to a maximum of 5 mg/kg/day until a SCORAD reduction of >or =35% was achieved ("treatment response"). After stopping CyA all patients entered a 4-week follow-up period. Cytokine secretion (IL-6, IL-8 and TNF-alpha) from patients' PBMC was assessed by ELISA before and after CyA treatment and was compared with 18 healthy nonatopic controls. Only the data of patients, who responded to CyA and did not experience a relapse during the follow-up period, were evaluated for this paper. RESULTS: Seven patients responded to CyA without relapse during the follow-up period. The median SCORAD index in these patients improved from 71 at baseline to 22 after CyA treatment (p < 0.001). AD patients' PBMC produced more IL-6, IL-8 and TNF-alpha than PBMC of controls. Suppression of IL-6 (p < 0.05) and IL-8 (p < 0.05) production was observed after CyA treatment. TNF-alpha levels were unchanged by CyA in all patients. CONCLUSIONS: The reduction in severity of pediatric AD with CyA is associated with decreased production of IL-6 and IL-8, but not TNF-alpha by PBMC.
Assuntos
Ciclosporina/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Imunossupressores/uso terapêutico , Interleucina-6/biossíntese , Interleucina-8/biossíntese , Fator de Necrose Tumoral alfa/biossíntese , Adolescente , Criança , Pré-Escolar , Ciclosporina/administração & dosagem , Dermatite Atópica/imunologia , Emulsões , Feminino , Humanos , Lactente , Masculino , Estudos ProspectivosAssuntos
Individualidade , Pessoalidade , Adesão a Diretivas Antecipadas , Diretivas Antecipadas , Direitos dos Animais , Animais , Confucionismo , Ética , Liberdade , Humanos , Relações Interpessoais , Obrigações Morais , Autonomia Pessoal , Filosofias Religiosas , Autoimagem , Responsabilidade Social , Valor da VidaRESUMO
BACKGROUND: Epidemiologic studies suggest an inverse correlation between infections and development of atopy. The purpose of this study was to test the hypothesis whether a preexisting Th1-type immune response elicited by BCG immunization could suppress allergic sensitization and airway hyperreactivity in an animal model. METHODS: BALB/c mice were immunized with BCG and/or sensitized to ovalbumin. RESULTS: BCG immunization alone resulted in cutaneous type-IV hypersensitivity reactions to tuberculin and granulomatous lesions in the liver. Splenic mononuclear cells (MNCs) produced increased levels of IFN-gamma after activation by Concanavalin A (ConA). Ovalbumin sensitization alone resulted in increased production of IL-4 after activation by ConA. Ovalbumin-sensitized animals also demonstrated markedly elevated anti-ovalbumin IgE/IgG1 serum antibody titers and increased airway reactivity after allergen challenges by means of the airways. BCG immunization 14 days before the start of ovalbumin sensitization markedly hindered the development of allergic responses as indicated by (1) increased IFN-gamma and normalized IL-4 and IL-10 production by splenic MNCs after activation with ConA, (2) a reduced proliferation rate of splenic MNCs after ovalbumin restimulation, (3) partial prevention of ovalbumin-specific IgE/IgG1 serum antibody titers but elevated (nonallergic) anti-ovalbumin IgG2a serum antibody titers, (4) prevention of airway responsiveness, (5) reduced eosinophilic influx into the airway lumen, and (6) reduced levels of IL-4 and IL-5 in broncho alveolar lavage fluids. CONCLUSION: In this model BCG immunization established a Th1-type immune response that hinders allergic sensitization and the development of increased airway reactivity.
Assuntos
Asma/imunologia , Vacina BCG/imunologia , Animais , Asma/fisiopatologia , Asma/prevenção & controle , Hiper-Reatividade Brônquica/prevenção & controle , Líquido da Lavagem Broncoalveolar/química , Modelos Animais de Doenças , Feminino , Hipersensibilidade Tardia/imunologia , Imunização , Interleucina-4/metabolismo , Interleucina-5/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Células Th1/fisiologiaRESUMO
The cAMP-dependent protein kinase (PKA) has been shown to play an important role in long-term potentiation (LTP) in the hippocampus, but little is known about the function of PKA in long-term depression (LTD). We have combined pharmacologic and genetic approaches to demonstrate that PKA activity is required for both homosynaptic LTD and depotentiation and that a specific neuronal isoform of type I regulatory subunit (RI beta) is essential. Mice carrying a null mutation in the gene encoding RI beta were established by use of gene targeting in embryonic stem cells. Hippocampal slices from mutant mice show a severe deficit in LTD and depotentiation at the Schaffer collateral-CA1 synapse. This defect is also evident at the lateral perforant path-dentate granule cell synapse in RI beta mutant mice. Despite a compensatory increase in the related RI alpha protein and a lack of detectable changes in total PKA activity, the hippocampal function in these mice is not rescued, suggesting a unique role for RI beta. Since the late phase of CA1 LTP also requires PKA but is normal in RI beta mutant mice, our data further suggest that different forms of synaptic plasticity are likely to employ different combinations of regulatory and catalytic subunits.