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1.
Expert Opin Biol Ther ; 20(9): 1061-1072, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32228250

RESUMO

INTRODUCTION: Treatment options for patients suffering from neuromyelitis optica spectrum disorders (NMOSD) so far have relied on off-label and empiric drugs. The first drug for the therapy of anti-aquaporin-4 (AQP4) antibody-seropositive NMOSD patients has been approved in 2019: the C5 complement inhibitor eculizumab. The interleukin-6 receptor inhibitor satralizumab and anti-CD19 antibody inebilizumab have published positive phase III trial results and await approval in the near future. AREAS COVERED: We sum up current treatment options and portray in detail the new developments in NMOSD drugs focusing on phase III clinical trials, followed by an overview of emerging drugs in less advanced clinical trial stages. EXPERT OPINION: Eculizumab's approval by the competent authorities marks a milestone in NMOSD treatment. Satralizumab and inebilizumab will most likely follow in approval given their presented results in efficacy and safety. All three drugs have shown efficacy in reducing relapse rates in NMOSD patients with anti-AQP4 antibodies. Although we will have even more evidence-based therapy options in the future, empirically used medications will keep their importance for now. The potential effect of new medications in AQP4 antibody-seronegative NMOSD and patients with an NMOSD phenotype and antibodies to myelin oligodendrocyte glycoprotein remains to be determined.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Neuromielite Óptica/tratamento farmacológico , Anticorpos Monoclonais Humanizados/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Antígenos CD19/imunologia , Aquaporina 4/imunologia , Autoanticorpos/imunologia , Humanos , Receptores de Interleucina-16/imunologia
2.
J Immunotoxicol ; 7(3): 183-93, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20307249

RESUMO

Interleukin-16 (IL-16) is a pro-inflammatory cytokine released by many types of cells found in the lungs, including normal airway and alveolar epithelial cells. Though a chemotactin for CD4(+) cells and eosinophils, IL-16 also modulates their production of factors that influence inflammatory lung diseases, e.g., asthma and allergic rhinitis. To date, little is known about any potential autocrine-like regulatory effects of IL-16. Using a model human alveolar basal epithelial A549 cell line, the present study sought to assess lung epithelial cell responses to IL-16. Potential induced effects on cell growth/function were assessed using MTT reduction, lactate dehydrogenase release, and 5-bromo-2-deoxyuridine incorporation assays. As IL-16 (at locally high levels) can induce CD4(+) cell death via apoptosis, this potential outcome among the A549 cells was also evaluated using TUNEL and changes in expression of caspase-3 and the pro-apoptotic and anti-apoptotic proteins of Bcl-2 family. The data here indicated that IL-16 inhibited A549 cell growth/function and this was associated with a marked increase in apoptosis characterized by DNA fragmentation, activation of caspase-3, and altered pro-apoptotic protein expression. Since lung epithelial cells lack the CD4 that may bind IL-16, it has been suggested that CD9 may act as an alternate receptor for this cytokine (i.e., an IL-16R). Thus, these studies also sought to determine the extent of CD9 expression on A549 cells and if any/all observed IL-16-induced changes were mediated by CD9. Flow cytometric analyses revealed the cells to be CD9(+)CD4(-). However, neutralization of the purported IL-16R with anti-CD9 antibody could not block the cytotoxic/growth inhibiting effects of IL-16. The only exception appeared to be a mitigation of a chemotactic effect of IL-16; however, studies with an equal amount of non-specific antibody (of same isotype as the anti-CD9) revealed this effect to be artefactual. The neutralization study results thus suggest to us that as-yet undefined pathway(s) exist through which IL-16 may act to exert growth inhibiting/apoptosis-inducing effects on A549 cells, a cell line routinely used as a model for lung epithelial cells.


Assuntos
Antígenos CD/metabolismo , Células Epiteliais/efeitos dos fármacos , Interleucina-16/farmacologia , Glicoproteínas de Membrana/metabolismo , Receptores de Interleucina-16/metabolismo , Anticorpos Bloqueadores/farmacologia , Antígenos CD/imunologia , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Regulação da Expressão Gênica , Humanos , Pulmão/patologia , Glicoproteínas de Membrana/imunologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptores de Interleucina-16/imunologia , Tetraspanina 29
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