RESUMO
Vitamin D is essential for the regulation of the immune system. In recent years, the role of vitamin D in the control of several autoimmune conditions such as inflammatory bowel disease (IBD), celiac disease, type 1 diabetes mellitus (T1DM), and others has been investigated. The aim of this review was to define the level of knowledge on vitamin D's role in these disorders, as well as the preventive and therapeutic role of vitamin D supplementation. Relevant studies published over the last 20 years were identified via a PubMed/Medline (http://www.ncbi.nlm.nih.gov/pubmed/) search using the keywords: vitamin D, autoimmune disease, and prevention. Vitamin D deficiency or impaired function of the enzymes necessary for its activity has been shown to affect the onset and severity of the autoimmune diseases examined. Vitamin D supplementation appears useful in the support therapy of IBD. Its role in celiac disease, autoimmune hepatitis, T1DM, and autoimmune thyroiditis is unclear. In conclusion, further studies are needed to define whether vitamin D is a cause or a result of the most common autoimmune, extra-skeletal diseases, such as IBD. Vitamin D should be provided to all newborns during their first year of life. Afterwards, the vitamin D supplementation regimen should be tailored to the presence of risk factors for vitamin D deficiency and/or specific disease.
Assuntos
Doenças Autoimunes , Doença Celíaca , Diabetes Mellitus Tipo 1 , Doenças Inflamatórias Intestinais , Deficiência de Vitamina D , Recém-Nascido , Humanos , Vitamina D/uso terapêutico , Diabetes Mellitus Tipo 1/prevenção & controle , Doença Celíaca/prevenção & controle , Doença Celíaca/complicações , Doença Celíaca/tratamento farmacológico , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/tratamento farmacológico , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/prevenção & controle , Doenças Autoimunes/etiologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/prevenção & controleRESUMO
Data from elderly Americans of an age of ≥50 years that were included in a large nationwide, randomized, double-blind, placebo-controlled prevention trial, show that vitamin D supplementation, alone or in combination with omega-3 fatty acids, reduces autoimmune disease risk with 22%. These Americans were treated with 2000 IU/day cholecalciferol (vitamin D) for a period of 5 years alone or in combination with 1g/day omega-3 fatty acids. Both treatments resulted in a significant reduction of the incidence of autoimmune diseases. The findings were more pronounced after two years after the start of the supplementation. Having a lower body index seems to be beneficial for the vitamin D effects. The question is via which pathophysiological mechanism(s) does vitamin D work. More and more of the secrets of the effects of vitamin D on the immune system and in particular on T cells are becoming identified and this study motivates to dig further.
Assuntos
Doenças Autoimunes , Ácidos Graxos Ômega-3 , Idoso , Doenças Autoimunes/prevenção & controle , Suplementos Nutricionais , Método Duplo-Cego , Ácidos Graxos Ômega-3/uso terapêutico , Humanos , Pessoa de Meia-Idade , Vitamina D/uso terapêutico , Vitaminas/uso terapêuticoRESUMO
OBJECTIVE: To investigate whether vitamin D and marine derived long chain omega 3 fatty acids reduce autoimmune disease risk. DESIGN: Vitamin D and omega 3 trial (VITAL), a nationwide, randomized, double blind, placebo controlled trial with a two-by-two factorial design. SETTING: Nationwide in the United States. PARTICIPANTS: 25 871 participants, consisting of 12 786 men ≥50 years and 13 085 women ≥55 years at enrollment. INTERVENTIONS: Vitamin D (2000 IU/day) or matched placebo, and omega 3 fatty acids (1000 mg/day) or matched placebo. Participants self-reported all incident autoimmune diseases from baseline to a median of 5.3 years of follow-up; these diseases were confirmed by extensive medical record review. Cox proportional hazard models were used to test the effects of vitamin D and omega 3 fatty acids on autoimmune disease incidence. MAIN OUTCOME MEASURES: The primary endpoint was all incident autoimmune diseases confirmed by medical record review: rheumatoid arthritis, polymyalgia rheumatica, autoimmune thyroid disease, psoriasis, and all others. RESULTS: 25 871 participants were enrolled and followed for a median of 5.3 years. 18 046 self-identified as non-Hispanic white, 5106 as black, and 2152 as other racial and ethnic groups. The mean age was 67.1 years. For the vitamin D arm, 123 participants in the treatment group and 155 in the placebo group had a confirmed autoimmune disease (hazard ratio 0.78, 95% confidence interval 0.61 to 0.99, P=0.05). In the omega 3 fatty acids arm, 130 participants in the treatment group and 148 in the placebo group had a confirmed autoimmune disease (0.85, 0.67 to 1.08, P=0.19). Compared with the reference arm (vitamin D placebo and omega 3 fatty acid placebo; 88 with confirmed autoimmune disease), 63 participants who received vitamin D and omega 3 fatty acids (0.69, 0.49 to 0.96), 60 who received only vitamin D (0.68, 0.48 to 0.94), and 67 who received only omega 3 fatty acids (0.74, 0.54 to 1.03) had confirmed autoimmune disease. CONCLUSIONS: Vitamin D supplementation for five years, with or without omega 3 fatty acids, reduced autoimmune disease by 22%, while omega 3 fatty acid supplementation with or without vitamin D reduced the autoimmune disease rate by 15% (not statistically significant). Both treatment arms showed larger effects than the reference arm (vitamin D placebo and omega 3 fatty acid placebo). STUDY REGISTRATION: ClinicalTrials.gov NCT01351805 and NCT01169259.
Assuntos
Doenças Autoimunes/epidemiologia , Colecalciferol/administração & dosagem , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Idoso , Doenças Autoimunes/prevenção & controle , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
This study aimed to investigate the dynamic effects of the traditional Chinese medicine compound Longdan Xiegan Decoction (LXD) on the inhibition of Notch signaling pathway activation and T helper (Th) cell differentiation in rats with experimental autoimmune uveitis (EAU). Based on a network pharmacology strategy, we conducted protein interaction network analysis to construct an active ingredient-disease treatment network. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were further used to screen out the possible signaling pathways regulated by LXD in the treatment of uveitis. In the subsequent functional studies, we established an EAU rat model and investigated the regulatory role of LXD in the Notch signaling pathway and Th cell differentiation in rats with EAU. Female Lewis rats were randomly divided into a normal control (NC) group, an EAU group, and an LXD group. After the induction of EAU, the ocular inflammation and pathological changes in the rats in each group were observed; for documentation, a scanning laser ophthalmoscope (SLO) was used to observe fundus inflammation on day 12 after immunization. Additionally, quantitative polymerase chain reaction (Q-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of Notch1, DLL4, IL-10 and IL-17A in the spleen, lymph nodes and ocular tissues of each group at 0, 6, 9, 12, 15 and 18 days after immunization. In addition, the dynamic frequencies of the CD4+, CD8+, Th17 and Treg cell subsets in the spleen, lymph nodes and ocular tissues were measured by flow cytometry. We found that the Notch signaling pathway was activated and the Th17 frequency was elevated in rats with EAU, leading to disrupted CD4+/CD8+ and Th17/Treg balance. The expression of Notch1, DLL4 and IL-17 mRNA and proteins in the EAU and LXD groups reached a peak on day 12, and then gradually decreased (all P < 0.05), and the ratios of the CD4+/CD8+ and Th17/Treg also peaked on day 12. However, after treatment with LXD, the expression of Notch1, DLL4 and IL-17 mRNA and proteins was significantly decreased (all P < 0.05), and the CD4+/CD8+ and Th17/Treg ratios significantly gradually returns to balance. LXD can efficiently inhibit Th17 cell differentiation, decrease inflammatory cytokine expression, and restore the CD4+/CD8+ and Th17/Treg balance by inhibiting the activation of the Notch signaling pathway in rats with EAU, thus effectively alleviating eye inflammation, protecting eye tissue structures, and positively regulating the immune state of the whole body and the intraocular microenvironment.
Assuntos
Anti-Inflamatórios/farmacologia , Doenças Autoimunes/prevenção & controle , Diferenciação Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Receptor Notch1/metabolismo , Células Th17/efeitos dos fármacos , Úvea/efeitos dos fármacos , Uveíte/prevenção & controle , Animais , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Mediadores da Inflamação/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Mapas de Interação de Proteínas , Ratos Endogâmicos Lew , Receptor Notch1/genética , Transdução de Sinais , Células Th17/imunologia , Células Th17/metabolismo , Úvea/imunologia , Úvea/metabolismo , Uveíte/genética , Uveíte/imunologia , Uveíte/metabolismoRESUMO
Experimental autoimmune uveitis (EAU) is a CD4+ T cell-mediated organ-specific autoimmune disease and has been considered as a model of human autoimmune uveitis. Dracocephalum heterophyllum (DH) is a Chinese herbal medicine used in treating hepatitis. DH suppressed the production of inflammatory cytokines through the recruitment of myeloid-derived suppressor cells (MDSCs) to the liver. However, it remains elusive whether DH can directly regulate CD4+ T cell biology and hence ameliorates the development of CD4+ T cell-mediated autoimmune disease. In the current study, we found that DH extract significantly suppressed the production of pro-inflammatory cytokines by CD4+ T cells. Further study showed that DH didn't affect the activation, differentiation, and apoptosis of CD4+ T cells. Instead, it significantly suppressed the proliferation of conventional CD4+ T cells both in vitro and in vivo. Mechanistic study showed that DH-treated CD4+ T cells were partially arrested at the G2/M phase of the cell cycle because of the enhanced inhibitory phosphorylation of Cdc2 (Tyr15). In addition, we demonstrated that treatment with DH significantly ameliorated EAU in mice through suppressing the proliferation of autoreactive antigen specific CD4+ T cells. Taken together, the current study indicates that DH-mediated suppression of CD4+ T cell proliferation may provide a promising therapeutic strategy for treating CD4+ T cell-mediated diseases.
Assuntos
Anti-Inflamatórios/farmacologia , Doenças Autoimunes/prevenção & controle , Linfócitos T CD4-Positivos/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Lamiaceae/química , Extratos Vegetais/farmacologia , Uveíte/prevenção & controle , Animais , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Doenças Autoimunes/patologia , Autoimunidade/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Proteína Quinase CDC2/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Camundongos Endogâmicos C57BL , Fosforilação , Transdução de Sinais , Úvea/efeitos dos fármacos , Úvea/imunologia , Úvea/metabolismo , Úvea/patologia , Uveíte/imunologia , Uveíte/metabolismo , Uveíte/patologiaRESUMO
To explore the mechanism of microRNA-155 (miR-155) deficiency, protecting against experimental autoimmune prostatitis (EAP) in a toll-like receptor 4 (TLR4)-dependent manner. After wild-type (WT) and miR-155-/- mice were injected with complete Freund's adjuvant and prostate antigen to establish EAP model, half were randomly selected for injection with lipopolysaccharide (LPS, a TLR4 ligand). The following experiments were then performed: von Frey filaments, hematoxylin-eosin (HE) staining, real time quantitative polymerase chain reaction (qRT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA). And the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the level of Malondialdehyde (MDA) were detected by corresponding kits.miR-155-/- mice with prostatitis exhibited the attenuated pelvic tactile allodynia/hyperalgesia and the suppressed TLR4/nuclear factor-kappa B (NF-κB) pathway as compared with the WT mice with prostatitis. In addition, LPS enhanced the upregulation of miR-155 and the activation of the TLR4/NF-κB pathway in the prostatic tissues of WT mice with EAP. Furthermore, prostatitis mice had aggravated inflammation scores accompanying the increased interleukin (IL)-1ß, tumor necrosis factor-α, IL-6, interferon-γ, IL-12, and MDA in prostatic tissues with the decreased IL-10, SOD and GSH-Px, and the unaltered IL-4. Compared with the mice from the WT + EAP group and the miR-155-/- + EAP + LPS group, mice from the miR-155-/- + EAP group had decreased inflammation and oxidative stress. miR-155 deficiency ameliorated pelvic tactile allodynia/hyperalgesia in EAP mice and improved inflammation and oxidative stress in prostatic tissues in a TLR4-dependent manner involving NF-κB activation, thereby exerting a therapeutic effect in chronic prostatitis treatment.
Assuntos
Doenças Autoimunes/genética , Hiperalgesia/genética , MicroRNAs/genética , NF-kappa B/genética , Prostatite/genética , Receptor 4 Toll-Like/genética , Animais , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/imunologia , Doenças Autoimunes/prevenção & controle , Modelos Animais de Doenças , Adjuvante de Freund/administração & dosagem , Regulação da Expressão Gênica , Glutationa Peroxidase/genética , Glutationa Peroxidase/imunologia , Hiperalgesia/induzido quimicamente , Hiperalgesia/imunologia , Hiperalgesia/prevenção & controle , Interferon gama/genética , Interferon gama/imunologia , Interleucina-12/genética , Interleucina-12/imunologia , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Lipopolissacarídeos/farmacologia , Masculino , Malondialdeído/imunologia , Malondialdeído/metabolismo , Camundongos , Camundongos Knockout , MicroRNAs/imunologia , NF-kappa B/imunologia , Estresse Oxidativo , Antígeno Prostático Específico/administração & dosagem , Prostatite/induzido quimicamente , Prostatite/imunologia , Prostatite/prevenção & controle , Transdução de Sinais , Superóxido Dismutase/genética , Superóxido Dismutase/imunologia , Receptor 4 Toll-Like/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologiaRESUMO
A number of studies have investigated primary and secondary prevention strategies for type 1 diabetes (T1D), since early interventions might improve long-term outcomes through the amelioration of immune processes and the preservation of beta-cell mass. Primary prevention trials focus on genetically at-risk individuals prior to the appearance of autoimmunity, whereas secondary prevention trials aim to halt the progression of complete beta-cell destruction in subjects with established islet autoimmunity (IA). Different approaches have been tested so far, focusing on both pharmaceutical (insulin and monoclonal antibodies) and non-pharmaceutical (vitamin D, omega-3 fatty acids, probiotics, and nicotinamide) interventions, as well as on environmental factors that are believed to trigger autoimmunity in T1D (cow's milk, gluten, and bovine insulin). Albeit certain strategies have displayed efficacy in reducing IA development rates, most efforts have been unsuccessful in preventing the onset of the disease in high-risk individuals. Moreover, significant heterogeneity in study designs, included populations, and explored outcomes renders the interpretation of study results challenging. The aim of this narrative review is to present and critically evaluate primary and secondary prevention strategies for T1D, seeking to fill existing knowledge gaps and providing insight into future directions.
Assuntos
Doenças Autoimunes/prevenção & controle , Diabetes Mellitus Tipo 1/prevenção & controle , Testes Genéticos , Prevenção Primária , Prevenção Secundária , Doenças Autoimunes/dietoterapia , Doenças Autoimunes/tratamento farmacológico , Diabetes Mellitus Tipo 1/dietoterapia , Diabetes Mellitus Tipo 1/tratamento farmacológico , HumanosRESUMO
The prevalence of autoimmune diseases (ADs) has increased over the past few decades. Vitamin D deficiency is a common factor in many of these diseases, whose etiology remains poorly understood. The objective of this study was to review published data on the role of vitamin D in ADs. Vitamin D insufficiency has been described as an important factor in the development of some ADs, generally attributed to the key role of this vitamin in the immune system. Most studies show that adequate supplementation can prevent and improve the development of some of these diseases, although the optimal vitamin D dose remains controversial. We highlight the importance of measuring serum vitamin D levels of the population and developing strategies to improve and maintain levels with no health risks.
Assuntos
Doenças Autoimunes/prevenção & controle , Suplementos Nutricionais , Deficiência de Vitamina D/complicações , Vitamina D/sangue , Vitaminas/sangue , Doenças Autoimunes/etiologia , Humanos , Vitamina D/administração & dosagem , Vitaminas/administração & dosagemRESUMO
PURPOSE: Selenium is frequently in nutraceuticals for pregnancy, given its role on fertility and thyroid metabolism. However, most evidence rise from non-controlled studies. We aimed to evaluate the protective effect of selenium against thyroid autoimmunity during and after pregnancy. METHODS: A multicenter, randomized, double-blind, placebo-controlled trial was performed and promoted by the Young Italian Endocrinologists Group (EnGioI)-Italian Society of Endocrinology. Forty-five women with thyroiditis in pregnancy were enrolled and randomly assigned to L-selenomethionine (L-Se-Met) 83 mcg/day or placebo (PLB) and evaluated at 10 ± 2 (T1), 36 ± 2 weeks of gestation (T2) and 6 months after delivery (postpartum, PP). RESULTS: We measured a significant reduction of autoantibodies after pregnancy in L-Se-Met group [at PP: TgAb 19.86 (11.59-52.60), p < 0.01; TPOAb 255.00 (79.00-292.00), p < 0.01], and an antibodies titer's rebound in PLB group (TgAb 151.03 ± 182.9, p < 0.01; TPOAb 441.28 ± 512.18, p < 0.01). A significant increase in selenemia was measured in L-Se-Met group at T2 (91.33 ± 25.49; p < 0.01) and PP (93.55 ± 23.53; p = 0.02). Two miscarriage occurred in PLB. No differences were found in thyroid volume, echogenicity, quality of life, maternal/fetal complications. CONCLUSIONS: SERENA study demonstrated a beneficial effect of L-Se-Met supplementation on autoantibody titer during pregnancy and on postpartum thyroiditis recurrence.
Assuntos
Doenças Autoimunes/prevenção & controle , Complicações na Gravidez/prevenção & controle , Selênio/uso terapêutico , Doenças da Glândula Tireoide/prevenção & controle , Oligoelementos/uso terapêutico , Adulto , Autoanticorpos/sangue , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Gravidez , Selênio/sangueRESUMO
Introdução: A esclerose múltipla (EM) é o distúrbio autoimune mais prevalente na atualidade e está associado à desmielinização dos neurônios no sistema nervoso central por meio da ativação do sistema imunológico. Estudos utilizando a vitamina A vêm se mostrando promissores na melhora da doença. Dessa forma, a presente dissertação tem como objetivo fornecer as melhores evidências disponíveis sobre o impacto clínico da vitamina A nos desfechos relacionados aos sintomas de pacientes portadores de EM. Métodos: Foi utilizado o formato de coletânea de artigos para a produção de dois artigos, sendo o primeiro um artigo de protocolo de revisão sistemática, usado como subsídio para a produção do segundo artigo, a revisão sistemática. Foram realizadas buscas no Pubmed, Embase, Scopus, Cinahl, Scielo, Web of science, Biblioteca cochrane e Science direct, de estudos que avaliassem a relação da suplementação de vitamina A e/ou concentrações séricas e os sintomas em pacientes portadores de EM. Para o delineamento da revisão sistemática foi utilizado o protocolo PRISMA. Para avaliar a qualidade metodológica dos estudos foi utilizada a escala JADAD para os ensaios clínicos randomizados e a NewcastleOttawa para os estudos observacionais. Para a extração de todos os dados encontrados foi criado um banco de dados no programa Microsoft Excel. Resultados: Na busca inicial encontramos 2053 estudos, e ao final das buscas foram selecionados 6 artigos elegíveis à pesquisa, sendo 2 Ensaios Clínicos Randomizados e 4 coortes. Dos seis estudos incluídos, dois utilizaram a suplementação de vitamina A e verificaram que a vitamina A é capaz de conter a progressão da doença nos membros superiores e as deficiências cognitivas, além de melhorar significativamente os escores de depressão, fadiga total e as três subescalas de fadiga (física, cognitiva e psicossocial). Os outros quatro estudos realizaram as dosagens das concentrações séricas da vitamina A e constataram que os níveis séricos de retinol não foram associados ao risco ou ao número de recidivas, nem ao agravamento da Escala de status Status de incapacidade Incapacidade expandida Expandida de Kurtzke. Porém, concentrações séricas elevadas de retinol foram associadas a menor da atividade da doença e foram capazes de predizer resultados de novas lesões por meio da ressonância magnética. Conclusão: as evidências identificadas no presente estudo permitem recomendar a suplementação de vitamina A como uma alternativa complementar ao tratamento da EM. Porém, novos ensaios clínicos controlados e bem realizados se fazem necessários para uma melhor definição da dosagem segura (AU).
Introduction: Multiple sclerosis (MS) is the most prevalent autoimmune disorder today and is associated with demyelination of neurons in the central nervous system through activation of the immune system. Studies using vitamin A have been promising to improve the disease. Thus, the present dissertation aims to provide the best available evidence on the clinical impact of vitamin A on the symptoms-related outcomes of patients with MS. Methods: The article collection format was used for the production of two articles. The first one was a systematic review protocol article, used as a subsidy for the production of the second article, the systematic review. We searched on Pubmed, Embase, Scopus, Cinahl, Scielo, Web of Science, Cochrane Library, and Science Direct for studies evaluating the relationship of vitamin A supplementation and/or serum concentrations and symptoms in MS patients. For the design of the systematic review the PRISMA protocol was used. To assess the methodological quality of the studies, the JADAD scale was used for randomized controlled trials and Newcastle-Ottawa for observational studies. To extract all the data found, a database was created in the Microsoft Excel program. Results: At the initial search we found 2053 studies, and at the end of the searches 6 articles were selected for the research (2 randomized clinical trials and 4 cohorts). Of the six studies included, two used vitamin A supplementation and found that vitamin A is capable of containing upper limb disease progression and cognitive impairment, as well as significantly improving depression, total fatigue, and all three subscales fatigue (physical, cognitive and psychosocial). The other four studies measured serum vitamin A concentrations and found it was not associated with risk or number of relapses or worsening of the Kurtzke Expanded Disability Expanded Disability Status Scale. However, elevated serum retinol concentrations were associated with lower disease activity and were able to predict results of new lesions by magnetic resonance imaging. Conclusion: evidence identified in this study allow to recommend supplementation of vitamin A as an additional alternative to the treatment of MS. However, new controlled clinical trials well done are needed to define safe dosing better (AU).
Assuntos
Vitamina A , Suplementos Nutricionais , Esclerose Múltipla/terapia , Doenças Autoimunes/prevenção & controleRESUMO
The autoimmune neurological disease, Multiple Sclerosis (MS), have increased at alarming rates in the Western society over the last few decades. While there are numerous efforts to develop novel treatment approaches, there is an unmet need to identify preventive strategies. We explored whether central nervous system (CNS) autoimmunity can be prevented through dietary manipulation using a spontaneous autoimmune encephalomyelitis mouse model. We report that the nutritional supplementation of non-fermentable fiber, common components of a vegetarian diet, in early adult life, prevents autoimmune disease. Dietary non-fermentable fiber alters the composition of the gut microbiota and metabolic profile with an increase in the abundance of long-chain fatty acids. Immune assays revealed that cecal extracts and a long chain fatty acid but not cecal lysates promoted autoimmune suppressive TH2 immune responses, demonstrating that non-fermentable fiber-induced metabolic changes account for the beneficial effects. Overall, these findings identify a non-invasive dietary strategy to prevent CNS autoimmunity and warrants a focus on nutritional approaches in human MS.
Assuntos
Fibras na Dieta/farmacologia , Encefalomielite Autoimune Experimental/prevenção & controle , Animais , Doenças Autoimunes/prevenção & controle , Sistema Nervoso Central/imunologia , Fibras na Dieta/uso terapêutico , Modelos Animais de Doenças , Ácidos Graxos/imunologia , Microbioma Gastrointestinal , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/microbiologia , Camundongos , Células Th2/imunologiaRESUMO
Since 2006, type 1 diabetes in Finland has plateaued and then decreased after the authorities' decision to fortify dietary milk products with cholecalciferol. The role of vitamin D in innate and adaptive immunity is critical. A statistical error in the estimation of the recommended dietary allowance (RDA) for vitamin D was recently discovered; in a correct analysis of the data used by the Institute of Medicine, it was found that 8895 IU/d was needed for 97.5% of individuals to achieve values ≥50 nmol/L. Another study confirmed that 6201 IU/d was needed to achieve 75 nmol/L and 9122 IU/d was needed to reach 100 nmol/L. The largest meta-analysis ever conducted of studies published between 1966 and 2013 showed that 25-hydroxyvitamin D levels <75 nmol/L may be too low for safety and associated with higher all-cause mortality, demolishing the previously presumed U-shape curve of mortality associated with vitamin D levels. Since all-disease mortality is reduced to 1.0 with serum vitamin D levels ≥100 nmol/L, we call public health authorities to consider designating as the RDA at least three-fourths of the levels proposed by the Endocrine Society Expert Committee as safe upper tolerable daily intake doses. This could lead to a recommendation of 1000 IU for children <1 year on enriched formula and 1500 IU for breastfed children older than 6 months, 3000 IU for children >1 year of age, and around 8000 IU for young adults and thereafter. Actions are urgently needed to protect the global population from vitamin D deficiency.
Assuntos
Erros de Medicação , Vitamina D/análogos & derivados , Adolescente , Doenças Autoimunes/mortalidade , Doenças Autoimunes/prevenção & controle , Causas de Morte , Criança , Pré-Escolar , Suplementos Nutricionais/normas , Finlândia/epidemiologia , Guias como Assunto , Humanos , Sistema Imunitário/metabolismo , Lactente , Síndrome Metabólica/mortalidade , Síndrome Metabólica/prevenção & controle , Saúde Pública , Vitamina D/administração & dosagem , Vitamina D/sangue , Vitamina D/normas , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/prevenção & controle , Adulto JovemRESUMO
Vitamin D (VitD) is a prohormone most noted for the regulation of calcium and phosphate levels in circulation, and thus of bone metabolism. Inflammatory and immune cells not only convert inactive VitD metabolites into calcitriol, the active form of VitD, but also express the nuclear receptor of VitD that modulates differentiation, activation and proliferation of these cells. In vitro, calcitriol upregulates different anti-inflammatory pathways and downregulates molecules that activate immune and inflammatory cells. Administration of VitD has beneficial effects in a number of experimental models of autoimmune disease. Epidemiologic studies have indicated that VitD insufficiency is frequently associated with immune disorders and infectious diseases, exacerbated by increasing evidence of suboptimal VitD status in populations worldwide. To date, however, most interventional studies in human inflammatory and immune diseases with VitD supplementation have proven to be inconclusive. One of the reasons could be that the main VitD metabolite measured in these studies was the 25-hydroxyVitD (25OHD) rather than its active form calcitriol. Although our knowledge of calcitriol as modulator of immune and inflammatory reactions has dramatically increased in the past decades, further in vivo and clinical studies are needed to confirm the potential benefits of VitD in the control of immune and inflammatory conditions.
Assuntos
Doenças Autoimunes/prevenção & controle , Imunidade/efeitos dos fármacos , Inflamação/prevenção & controle , Vitamina D/administração & dosagem , Vitamina D/imunologia , Animais , Doenças Autoimunes/imunologia , Humanos , Imunidade/imunologia , Inflamação/imunologiaRESUMO
Andrographis paniculata has long been part of the traditional herbal medicine system in Asia and in Scandinavia. Andrographolide was isolated as a major bioactive constituent of A. paniculata in 1951, and since 1984, andrographolide and its analogs have been scrutinized with modern drug discovery approach for anti-inflammatory properties. With this accumulated wealth of pre-clinical data, it is imperative to review and consolidate different sources of information, to decipher the major anti-inflammatory mechanisms of action in inflammatory diseases, and to provide direction for future studies. Andrographolide and its analogs have been shown to provide anti-inflammatory benefits in a variety of inflammatory disease models. Among the diverse signaling pathways investigated, inhibition of NF-κB activity is the prevailing anti-inflammatory mechanism elicited by andrographolide. There is also increasing evidence supporting endogenous antioxidant defense enhancement by andrographolide through Nrf2 activation. However, the exact pathway leading to NF-κB and Nrf2 activation by andrographolide has yet to be elucidated. Validation and consensus on the major mechanistic actions of andrographolide in different inflammatory conditions are required before translating current findings into clinical settings. There are a few clinical trials conducted using andrographolide in fixed combination formulation which have shown anti-inflammatory benefits and good safety profile. A concerted effort is definitely needed to identify potent andrographolide lead compounds with improved pharmacokinetics and toxicological properties. Taken together, andrographolide and its analogs have great potential to be the next new class of anti-inflammatory agents, and more andrographolide molecules are likely moving towards clinical study stage in the near future.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Diterpenos/uso terapêutico , Desenho de Fármacos , Drogas em Investigação/uso terapêutico , Modelos Biológicos , Subunidade p50 de NF-kappa B/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Doenças Autoimunes/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/imunologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Dermatite/tratamento farmacológico , Dermatite/imunologia , Dermatite/metabolismo , Dermatite/prevenção & controle , Diterpenos/efeitos adversos , Diterpenos/química , Diterpenos/farmacologia , Drogas em Investigação/efeitos adversos , Drogas em Investigação/química , Drogas em Investigação/farmacologia , Hepatite/tratamento farmacológico , Hepatite/imunologia , Hepatite/metabolismo , Hepatite/prevenção & controle , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/imunologia , Cirrose Hepática/metabolismo , Cirrose Hepática/prevenção & controle , Fator 2 Relacionado a NF-E2/agonistas , Fator 2 Relacionado a NF-E2/metabolismo , Subunidade p50 de NF-kappa B/química , Subunidade p50 de NF-kappa B/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/imunologia , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Pneumonia/tratamento farmacológico , Pneumonia/imunologia , Pneumonia/metabolismo , Substâncias Protetoras/química , Substâncias Protetoras/metabolismo , Substâncias Protetoras/uso terapêuticoRESUMO
The development of autoimmunity and/or autoimmune diseases is multifactorial. Vitamin D is one of the factors that might play a role. We postulated that both the presence of adjuvants and insufficient levels of vitamin D may result in the development of autoimmunity in patients with autoimmune/inflammatory syndrome induced by adjuvants (ASIA) in relation to silicone implant incompatibility. We measured vitamin D levels in 135 patients with ASIA in relation to silicone implant incompatibility and related findings to the presence of autoantibodies that are commonly used to diagnose systemic autoimmune diseases. Furthermore, we systematically reviewed the literature regarding vitamin D deficiency as a risk factor for the development of autoantibodies. Vitamin D measurements were available for analysis in 131 of 135 patients with ASIA in relation to SIIS. Twenty-three patients (18%) tested positive for autoantibodies, from which 18 patients (78%) had either a vitamin D deficiency or insufficiency (median vitamin D level 60.5 mmol/L), whereas five patients (22%) had sufficient vitamin D levels. The risk to develop autoantibodies was significantly increased in vitamin D deficient and/or insufficient patients [RR 3.14; 95% CI, 1.24-7.95; p = 0.009]. Reviewed literature suggested an association between vitamin D levels and the presence and/or titer levels of autoantibodies in different autoimmune diseases. From our current study and from our review of the literature, we conclude that vitamin D deficiency is related to the presence of autoantibodies. Whether vitamin D supplementation results in a decrease of autoimmunity needs to be studied prospectively.
Assuntos
Autoanticorpos/imunologia , Doenças Autoimunes/etiologia , Implantes de Mama/efeitos adversos , Elastômeros de Silicone/efeitos adversos , Deficiência de Vitamina D/complicações , Vitamina D/uso terapêutico , Doenças Autoimunes/imunologia , Doenças Autoimunes/prevenção & controle , Estudos de Coortes , Suplementos Nutricionais , Feminino , Humanos , Fatores de Risco , Deficiência de Vitamina D/tratamento farmacológico , Deficiência de Vitamina D/imunologia , Vitaminas/uso terapêuticoRESUMO
In the last few years, more attention has been given to the "non-calcemic" effect of vitamin D. Several observational studies and meta-analyses demonstrated an association between circulating levels of vitamin D and outcome of many common diseases, including endocrine diseases, chronic diseases, cancer progression, and autoimmune diseases. In particular, cells of the immune system (B cells, T cells, and antigen presenting cells), due to the expression of 1α-hydroxylase (CYP27B1), are able to synthesize the active metabolite of vitamin D, which shows immunomodulatory properties. Moreover, the expression of the vitamin D receptor (VDR) in these cells suggests a local action of vitamin D in the immune response. These findings are supported by the correlation between the polymorphisms of the VDR or the CYP27B1 gene and the pathogenesis of several autoimmune diseases. Currently, the optimal plasma 25-hydroxyvitamin D concentration that is necessary to prevent or treat autoimmune diseases is still under debate. However, experimental studies in humans have suggested beneficial effects of vitamin D supplementation in reducing the severity of disease activity. In this review, we summarize the evidence regarding the role of vitamin D in the pathogenesis of autoimmune endocrine diseases, including type 1 diabetes mellitus, Addison's disease, Hashimoto's thyroiditis, Graves' disease and autoimmune polyendocrine syndromes. Furthermore, we discuss the supplementation with vitamin D to prevent or treat autoimmune diseases.
Assuntos
Doenças Autoimunes/etiologia , Doenças do Sistema Endócrino/etiologia , Vitamina D/fisiologia , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , Doença de Addison/sangue , Doença de Addison/epidemiologia , Doença de Addison/genética , Animais , Doenças Autoimunes/sangue , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/prevenção & controle , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/genética , Doenças do Sistema Endócrino/sangue , Doenças do Sistema Endócrino/epidemiologia , Doença de Graves/sangue , Doença de Graves/epidemiologia , Doença de Graves/genética , Humanos , Polimorfismo Genético , Receptores de Calcitriol/genética , Vitamina D/administração & dosagem , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/dietoterapia , Deficiência de Vitamina D/epidemiologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Triptolide is a most important active ingredient extracted from traditional Chinese medicine Tripterygium, which has been widely used to treat glomerulonephritis as well as immune-mediated disorders, likely for its immunosuppressive, anti-proliferative and anti-inflammatory effects. AIM OF THE STUDY: In this study, we have investigated the potential protective effects of triptolide against diabetic cardiomyopathy (DCM) by regulating immune system, attenuating inflammatory response, thus resulting in decreased cardiac fibrosis and improved left ventricle function. MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into 5 groups: normal group, diabetic group and diabetic rats treated with triptolide (50, 100, or 200µg/kg/day resp) for 8 weeks. Cardiac function was performed by echocardiography and histopathology of the hearts was examined with HE, Masson staining and scanning electron microscopy. Immune regulation mediator, macrophage infiltration, inflammatory response and cardiac fibrosis related cytokines were measured by RT-PCR, Western blot and Immunohistochemistry staining. RESULTS: In the diabetic group, the expressions of TLR4 and NF-κB p65 were both up-regulated, which was associated with increased pro-inflammatory cytokines, coupled with cardiac fibrosis and impaired left ventricular function. Interestingly, pathological structure and function of left ventricle were both significantly improved in the triptolide treated groups. Furthermore, the immune mediator TLR4, downstream activator NF-κB p65, macrophage infiltration (CD68+), pro-inflammatory cytokines (TNF-α, IL-1ß), cell adhesion molecule (VCAM-1) and chemokine (MCP-1) were significantly suppressed when treated with medium and high dosage triptolide compared with the diabetic group. Moreover, cardiac fibrosis pathway including α-SMA, TGF-ß1, vimentin and collagen accumulations were observed significantly decreased in the triptolide treated groups. CONCLUSIONS: Our data demonstrated that the protective effects of triptolide against DCM might attribute to inhibition of TLR4-induced NF-κB/IL-1ß immune pathway, suppression of NF-κB/TNF-α/VCAM-1 inflammatory pathway and down-regulation of TGF-ß1/α-SMA/Vimentin fibrosis pathway.
Assuntos
Doenças Autoimunes/prevenção & controle , Cardiomiopatias/prevenção & controle , Cardiomiopatias Diabéticas/complicações , Diterpenos/farmacologia , Inflamação/prevenção & controle , Fenantrenos/farmacologia , Receptor 4 Toll-Like/fisiologia , Animais , Doenças Autoimunes/complicações , Glicemia/metabolismo , Cardiomiopatias/complicações , Compostos de Epóxi/farmacologia , Fibrose , Testes de Função Cardíaca/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Inflamação/complicações , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Prostatitis is a common disease contributing to 8% of all urologist visits. Yet the etiology and effective treatment remain to be further elucidated. Using a non-obese diabetes mouse model that can be induced by autoimmune response for the spontaneous development of prostatitis, we found that injection of the ASC-J9® at 75 mg/Kg body weight/48 hours led to significantly suppressed prostatitis that was accompanied with reduction of lymphocyte infiltration with reduced CD4+ T cells in prostate. In vitro studies with a co-culture system also confirmed that ASC-J9® treatment could suppress the CD4+ T cell migration to prostate stromal cells. Mechanisms dissection indicated that ASC-J9® can suppress CD4+ T cell migration via decreasing the cytokine CCL2 in vitro and in vivo, and restoring CCL2 could interrupt the ASC-J9® suppressed CD4+ T cell migration. Together, results from in vivo and in vitro studies suggest that ASC-J9® can suppress prostatitis by altering the autoimmune response induced by CD4+ T cell recruitment, and using ASC-J9® may help us to develop a potential new therapy to battle the prostatitis with little side effects.