RESUMO
INTRODUCTION: Epstein-Barr virus (EBV/HHV-4) has been implicated in the pathogenesis of multiple sclerosis (MS). This study was conducted to investigate the levels of pro-inflammatory cytokines IL-1ß and IL-6 in healthy EBV carriers and MS patients with prior EBV infection in response to treatment with EBV nuclear antigen 1 (EBNA-1) and replication and transcription activator (BRLF-1/Rta) peptide antigens in whole blood cell culture to assess the cytokine expression across all cells in the peripheral blood. METHODS: Isolated whole blood cells from the included participants were incubated at a concentration of 106 cells/mL with BRLF-1 or EBNA-1. The amount of IL-1ß and IL-6 transcripts were measured with quantitative RT-PCR at day 3 after incubation. MTT assay was conducted to examine cytotoxicity of the peptides and their effect on cell viability. Changes in cytokine expression and cell viability were analyzed using one-way and two-way ANOVA, respectively. RESULTS: Ten MS patients and ten healthy donors were enrolled in the study. Treatment with the peptide antigens resulted in increased cytokines expression in both MS patients and healthy subjects. Furthermore, IL-1ß levels were higher in MS patients compared to healthy EBV carriers. MTT assay revealed no significant difference in cell viability between the two groups. DISCUSSION: The higher levels of IL-1ß in response to EBV antigens in MS patients may reflect the host neuroinflammatory environment and support the notion that immune response against EBV has a role as an aggravating factor in the progression of MS by contributing to the neuroinflammatory cascade.
Assuntos
Infecções por Vírus Epstein-Barr , Antígenos Nucleares do Vírus Epstein-Barr , Proteínas Imediatamente Precoces , Esclerose Múltipla , Transativadores , Citocinas/metabolismo , Infecções por Vírus Epstein-Barr/complicações , Antígenos Nucleares do Vírus Epstein-Barr/imunologia , Herpesvirus Humano 4 , Humanos , Proteínas Imediatamente Precoces/imunologia , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Esclerose Múltipla/tratamento farmacológico , Transativadores/imunologiaRESUMO
BACKGROUND: Vaccination against HCV is an effective measure in reduction of virus-related public health burden and mortality. However, no prophylactic vaccine is available as of yet. DNA-based immunization is a promising modality to generate cellular and humoral immune responses. The objective of this study is to provide a systematic review of HCV DNA vaccines and investigate and discuss the strategies employed to optimize their efficacies. METHODS: MEDLINE (PubMed), Web of Science, Scopus, ScienceDirect, and databases in persian language including the Regional Information Centre for Science & Technology (RICeST), the Scientific Information Database and the Iranian Research Institute for Information Science and Technology (IranDoc) were examined to identify studies pertaining to HCV nucleic acid vaccine development from 2000 to 2020. RESULTS: Twenty-seven articles were included. Studies related to HCV RNA vaccines were yet to be published. A variety of strategies were identified with the potential to optimize HCV DNA vaccines such as incorporating multiple viral proteins and molecular tags such as HBsAg and Immunoglobulin Fc, multi-epitope expression, co-expression plasmid utilization, recombinant subunit immunogens, heterologous prime-boosting, incorporating NS3 mutants in DNA vaccines, utilization of adjuvants, employment of less explored methods such as Gene Electro Transfer, construction of multi- CTL epitopes, utilizing co/post translational modifications and polycistronic genes, among others. The effectiveness of the aforementioned strategies in boosting immune response and improving vaccine potency was assessed. CONCLUSIONS: The recent progress on HCV vaccine development was examined in this systematic review to identify candidates with most promising prophylactic and therapeutic potential.
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Hepatite C , Vacinas de DNA , Vacinas contra Hepatite Viral , Animais , Hepacivirus/genética , Humanos , Irã (Geográfico) , Camundongos , Camundongos Endogâmicos BALB C , Vacinas de DNA/genética , Vacinas contra Hepatite Viral/genéticaRESUMO
INTRODUCTION: Epstein-Barr virus (EBV), a double-stranded DNA virus, has 2 phases of lytic and latent infection in host cells. After infecting B lymphocytes, EBV becomes persistent in these cells. In healthy individuals, T lymphocytes play a key role in killing EBV-infected B cells. Statistical studies have shown that symptomatic EBV infection increases the risk of MS. METHODS: This study intended to measure the immune system's response against the different components of EBV, focusing particularly on T lymphocytes' reaction. Consequently, the mRNA level of IL-2 and IFN-γ, liable for impressing autoimmune diseases and as indicators of T-cell function, was compared in EBNA1- and BRLF1-treated whole blood (WB) cultures of 10 healthy individuals and 10 MS patients using real-time RT-PCR. RESULTS: The analysis of the results demonstrated a significant increased level of IL-2 in MS patients than healthy subjects after exposure to both peptides. Also, the mRNA level of IFN-γ increased in MS patients in EBNA1-treated WB culture. CONCLUSION: According to the study's results, EBV peptides can reactivate immune cells, especially T lymphocytes, and may indirectly induce inflammation and develop MS; however, it seems that long-time exposure to these peptides has reducing effect on T-cell function and faces the control of infected B lymphocytes with difficulties.
Assuntos
Infecções por Vírus Epstein-Barr , Esclerose Múltipla , Herpesvirus Humano 4 , Humanos , Interferon gama , Interleucina-2 , Linfócitos TRESUMO
INTRODUCTION: Eosinophilic granulomatosis with polyangiitis (EGPA) was formerly known as Churg-Strauss syndrome. The condition is characterized by disseminated necrotizing vasculitis with extravascular granulomas associated with hypereosinophilia. The vasculitides affect small vessels and are associated with antineutrophil cytoplasmic antibodies (ANCAs) detectable in the blood. Distinguishing between type 2-mediated chronic airway inflammation such as chronic rhinosinusitis with nasal polyps (CRSwNP) without vasculitis can be clinically challenging and should be considered. MATERIALS AND METHODS: Immunological background, diagnosis, and therapy of EGPA were identified through literature searches in Medline, PubMed, as well as national and international studies (ClinicalTrials.gov) and the Cochrane Library. Human studies published up to and including 10/2023 on the topic were considered. RESULTS: In cases of deteriorating general health with previously known eosinophilic inflammation of the upper and lower airways, EGPA and its interdisciplinary investigation should be considered. Various types of eosinophilic inflammation and syndromes must be considered differentially. CONCLUSION: Characterization of mucosal airway inflammation through biomarker determination is meaningful and occasionally makes the difference for targeted therapy.