RESUMO
Anti-viral monoclonal antibody (mAb) treatments may provide immediate but short-term immunity from coronavirus disease 2019 (COVID-19) in high-risk populations, such as people with diabetes and the elderly; however, data on their efficacy in these populations are limited. We demonstrate that prophylactic mAb treatment blocks viral replication in both the upper and lower respiratory tracts in aged, type 2 diabetic rhesus macaques. mAb infusion dramatically curtails severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated stimulation of interferon-induced chemokines and T cell activation, significantly reducing development of interstitial pneumonia. Furthermore, mAb infusion significantly dampens the greater than 3-fold increase in SARS-CoV-2-induced effector CD4 T cell influx into the cerebrospinal fluid. Our data show that neutralizing mAbs administered preventatively to high-risk populations may mitigate the adverse inflammatory consequences of SARS-CoV-2 exposure.
Assuntos
Anticorpos Monoclonais/uso terapêutico , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Envelhecimento/imunologia , Animais , COVID-19/líquido cefalorraquidiano , COVID-19/complicações , COVID-19/imunologia , Complicações do Diabetes/imunologia , Complicações do Diabetes/virologia , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/imunologia , Feminino , Humanos , Ativação Linfocitária , Macaca mulatta , Masculino , Neurite (Inflamação)/imunologia , Neurite (Inflamação)/prevenção & controle , Profilaxia Pré-Exposição , Linfócitos T/imunologia , Replicação Viral/imunologiaRESUMO
BACKGROUNDCytotoxic T lymphocyte antigen 4 (CTLA4) is essential for immune homeostasis. Genetic mutations causing haploinsufficiency (CTLA4h) lead to a phenotypically heterogenous, immune-mediated disease that can include neuroinflammation. The neurological manifestations of CTLA4h are poorly characterized.METHODSWe performed an observational natural history study of 50 patients with CTLA4h who were followed at the NIH. We analyzed clinical, radiological, immunological, and histopathological data.RESULTSEvidence for neuroinflammation was observed in 32% (n = 16 of 50) of patients in this cohort by magnetic resonance imaging (MRI) and/or by cerebrospinal fluid analysis. Clinical symptoms were commonly absent or mild in severity, with headaches as the leading complaint (n = 13 of 16). The most striking findings were relapsing, large, contrast-enhancing focal lesions in the brain and spinal cord observed on MRI. We detected inflammation in the cerebrospinal fluid and leptomeninges before the parenchyma. Brain biopsies of inflammatory lesions from 10 patients showed perivascular and intraparenchymal mixed cellular infiltrates with little accompanying demyelination or neuronal injury.CONCLUSIONSNeuroinflammation due to CTLA4h is mediated primarily by an infiltrative process with a distinct and striking dissociation between clinical symptoms and radiological findings in the majority of patients.FUNDINGNIAID, NIH, Division of Intramural Research, NINDS, NIH, Division of Intramural Research, and the National Multiple Sclerosis Society-American Brain Foundation.TRIAL REGISTRATIONClinicalTrials.gov NCT00001355.
Assuntos
Antígeno CTLA-4/deficiência , Doenças do Sistema Nervoso Central/etiologia , Haploinsuficiência , Neurite (Inflamação)/etiologia , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Antígeno CTLA-4/genética , Antígeno CTLA-4/imunologia , Doenças do Sistema Nervoso Central/genética , Doenças do Sistema Nervoso Central/imunologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neurite (Inflamação)/genética , Neurite (Inflamação)/imunologia , Neuroimagem , Neuroimunomodulação , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologia , Adulto JovemRESUMO
Immunosuppressed patients are at higher risk for developing herpes zoster (HZ), and neurological complications are frequent in them. However, the influence of immunosuppression (IS) on the severity and prognosis of neurological complications of varicella-zoster virus (VZV) reactivation is unknown. We studied retrospectively patients with neurological complications due to VZV reactivation who attended our hospital between 2004 and 2019. We aimed to assess the clinical spectrum, potential prognostic factors, and the influence of the immune status on the severity of neurological symptoms. A total of 98 patients were included (40% had IS). Fifty-five patients (56%) had cranial neuropathies which included Ramsay-Hunt syndrome (36 patients) and cranial multineuritis (23 patients). Twenty-one patients developed encephalitis (21%). Other diagnosis included radiculopathies, meningitis, vasculitis, or myelitis (15, 10, 6, and 4 patients, respectively). Mortality was low (3%). At follow-up, 24% of patients had persistent symptoms although these were usually mild. IS was associated with severity (defined as a modified Rankin scale greater than 2) (odds ratio, 4.23; 95% confidence interval, 1.74-10.27), but not with prognosis. Shorter latency between HZ and neurologic symptoms was the only factor associated with an unfavorable course (death or sequelae) (odds ratio, 0.82; 95% confidence interval, 0.71-0.95). In conclusion, the clinical spectrum of neurological complications in VZV reactivation is wide. Mortality was low and sequelae were mild. The presence of IS may play a role on the severity of neurological symptoms, and a shorter time between HZ and the onset of neurological symptoms appears to be a negative prognostic factor.
Assuntos
Encefalite por Varicela Zoster/imunologia , Herpes Zoster da Orelha Externa/imunologia , Herpes Zoster/imunologia , Herpesvirus Humano 3/patogenicidade , Imunossupressores/efeitos adversos , Neurite (Inflamação)/imunologia , Radiculopatia/imunologia , Idoso , Idoso de 80 Anos ou mais , Encefalite por Varicela Zoster/complicações , Encefalite por Varicela Zoster/diagnóstico , Encefalite por Varicela Zoster/mortalidade , Feminino , Herpes Zoster/complicações , Herpes Zoster/diagnóstico , Herpes Zoster/mortalidade , Herpes Zoster da Orelha Externa/diagnóstico , Herpes Zoster da Orelha Externa/etiologia , Herpes Zoster da Orelha Externa/mortalidade , Humanos , Terapia de Imunossupressão , Masculino , Meningite Viral/diagnóstico , Meningite Viral/etiologia , Meningite Viral/imunologia , Meningite Viral/mortalidade , Pessoa de Meia-Idade , Mielite/diagnóstico , Mielite/etiologia , Mielite/imunologia , Mielite/mortalidade , Neurite (Inflamação)/diagnóstico , Neurite (Inflamação)/etiologia , Neurite (Inflamação)/mortalidade , Prognóstico , Radiculopatia/diagnóstico , Radiculopatia/etiologia , Radiculopatia/mortalidade , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida , Vasculite/diagnóstico , Vasculite/etiologia , Vasculite/imunologia , Vasculite/mortalidade , Ativação Viral/efeitos dos fármacos , Latência Viral/efeitos dos fármacosRESUMO
OBJECTIVE: To report 2 patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who presented acutely with Miller Fisher syndrome and polyneuritis cranialis, respectively. METHODS: Patient data were obtained from medical records from the University Hospital "Príncipe de Asturias," Alcalá de Henares, and the University Hospital "12 de Octubre," Madrid, Spain. RESULTS: A 50-year-old man presented with anosmia, ageusia, right internuclear ophthalmoparesis, right fascicular oculomotor palsy, ataxia, areflexia, albuminocytologic dissociation, and positive testing for anti-GD1b-immunoglobulin G antibody. Five days previously, he had developed a cough, malaise, headache, low back pain, and fever. A 39-year-old man presented with ageusia, bilateral abducens palsy, areflexia, and albuminocytologic dissociation. Three days previously, he had developed diarrhea, a low-grade fever, and poor general condition. Oropharyngeal swab test for SARS-CoV-2 by qualitative real-time reverse transcriptase PCR assay was positive in both patients and negative in the CSF. The first patient was treated with IV immunoglobulin and the second with acetaminophen. Two weeks later, both patients made a complete neurologic recovery, except for residual anosmia and ageusia in the first case. CONCLUSIONS: Our 2 cases highlight the rare occurrence of Miller Fisher syndrome and polyneuritis cranialis during the coronavirus disease 2019 (COVID-19) pandemic. These neurologic manifestations may occur because of an aberrant immune response to COVID-19. The full clinical spectrum of neurologic symptoms in patients with COVID-19 remains to be characterized.
Assuntos
Infecções por Coronavirus/fisiopatologia , Doenças dos Nervos Cranianos/fisiopatologia , Síndrome de Miller Fisher/fisiopatologia , Neurite (Inflamação)/fisiopatologia , Pneumonia Viral/fisiopatologia , Adulto , Ageusia/etiologia , Ageusia/fisiopatologia , Betacoronavirus , COVID-19 , Infecções por Coronavirus/complicações , Doenças dos Nervos Cranianos/etiologia , Doenças dos Nervos Cranianos/imunologia , Gangliosídeos/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Miller Fisher/etiologia , Síndrome de Miller Fisher/imunologia , Neurite (Inflamação)/etiologia , Neurite (Inflamação)/imunologia , Transtornos do Olfato/etiologia , Transtornos do Olfato/fisiopatologia , Pandemias , Pneumonia Viral/complicações , SARS-CoV-2 , Índice de Gravidade de Doença , EspanhaRESUMO
Autoantibody against myelin oligodendrocyte glycoprotein (MOG) has been reported in a range of demyelinating neurological entities. Recent studies demonstrate a wider spectrum of MOG-IgG-associated disorders with the discovery of MOG-IgG-positive brainstem encephalitis, cortical encephalitis, and cranial nerve involvement with concurrent central nervous system involvement. We present a MOG-IgG-positive pediatric patient diagnosed with isolated oculomotor neuritis without concurrent central nervous system neuroimaging lesions, in the absence of a demyelinating event. Brain MRI shows swelling and gadolinium enhancement of the left oculomotor nerve at the cisternal segment. This is the first report to demonstrate MOG-IgG seropositivity in isolated cranial nerve lesions. This case may expand the clinical phenotype of MOG-IgG-associated diseases, and clinicians should not hesitate to test for MOG-IgG in cases with neuroimaging features of cranial neuritis alone.
Assuntos
Glicoproteína Mielina-Oligodendrócito/imunologia , Neurite (Inflamação)/diagnóstico , Doenças do Nervo Oculomotor/diagnóstico , Doenças do Nervo Oculomotor/imunologia , Pré-Escolar , Feminino , Humanos , Imageamento por Ressonância Magnética , Neurite (Inflamação)/imunologia , Neurite (Inflamação)/patologia , Doenças do Nervo Oculomotor/patologia , FenótipoRESUMO
BACKGROUND: Yokukansan is a traditional Japanese herbal medicine that has an antiallodynic effect in patients with chronic pain. However, the mechanisms by which yokukansan inhibits neuropathic pain are unclear. OBJECTIVE: This study aimed to investigate the molecular effects of yokukansan on neuroinflammation in U373 MG glioblastoma astrocytoma cells, which express a functional high-affinity neurokinin 1 receptor (substance P receptor), and produce interleukin (IL)-6 and IL-8 in response to stimulation by substance P (SP). METHODS: We assessed the effect of yokukansan on the expression of ERK1/2, P38 MAPK, nuclear factor (NF)-κB, and cyclooxygenase-2 (COX-2) in U373 cells by western blot assay. Levels of IL-6 and IL-8 in conditioned medium obtained after stimulation of cells with SP for 24 h were measured by enzyme-linked immunosorbent assay. All experiments were conducted in triplicate. Results were analyzed by one-way ANOVA, and significance was accepted at p < 0.05. RESULTS: Yokukansan suppressed SP-induced production of IL-6 and IL-8 by U373 MG cells, and downregulated SP-induced COX-2 expression. Yokukansan also inhibited phosphorylation of ERK1/2 and p38 MAPK, as well as nuclear translocation of NF-κB, induced by SP stimulation of U373 MG cells. CONCLUSION: Yokukansan exhibits anti-inflammatory activity by suppressing SP-induced production of IL-6 and IL-8 and downregulating COX-2 expression in U373 MG cells, possibly via inhibition of the activation of signaling molecules, such as ERK1/2, p38 MAPK, and NF-κB.
Assuntos
Neoplasias Encefálicas/patologia , Medicamentos de Ervas Chinesas/farmacologia , Glioblastoma/patologia , Neurite (Inflamação)/prevenção & controle , Substância P/farmacologia , Anti-Inflamatórios/farmacologia , Astrocitoma/imunologia , Astrocitoma/metabolismo , Astrocitoma/patologia , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Glioblastoma/imunologia , Glioblastoma/metabolismo , Interações Ervas-Drogas , Medicina Herbária , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Japão , Neurite (Inflamação)/induzido quimicamente , Neurite (Inflamação)/imunologia , Neurite (Inflamação)/metabolismo , Neuroimunomodulação/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Transdução de Sinais/efeitos dos fármacosRESUMO
The systemic regulation of immune reactions by the nervous system is well studied and depends on the release of hormones. Some regional regulations of immune reactions, on the other hand, depend on specific neural pathways. Better understanding of these regulations will expand therapeutic applications for neuroimmune and organ-to-organ functional interactions. Here, we discuss one regional neuroimmune interaction, the gateway reflex, which converts specific neural inputs into local inflammatory outputs in the CNS. Neurotransmitters released by the inputs stimulate specific blood vessels to express chemokines, which serve as a gateway for immune cells to extravasate into the target organ such as the brain or spinal cord. Several types of gateway reflexes have been reported, and each controls distinct CNS blood vessels to form gateways that elicit local inflammation, particularly in the presence of autoreactive immune cells. For example, neural stimulation by gravity creates the initial entry point to the CNS by CNS-reactive pathogenic CD4+ T cells at the dorsal vessels of fifth lumbar spinal cord, while pain opens the gateway at the ventral side of blood vessels in the spinal cord. In addition, it was recently found that local inflammation by the gateway reflex in the brain triggers the activation of otherwise resting neural circuits to dysregulate organ functions in the periphery including the upper gastrointestinal tract and heart. Therefore, the gateway reflex represents a novel bidirectional neuroimmune interaction that regulates organ functions and could be a promising target for bioelectric medicine.
Assuntos
Sistema Nervoso Central/imunologia , Sistema Imunitário/fisiologia , Neurite (Inflamação)/imunologia , Neurotransmissores/imunologia , Animais , Encéfalo/imunologia , Citocinas/imunologia , Gravitação , Humanos , Sistema Imunitário/citologia , Camundongos , Vias Neurais/imunologia , Neuroimunomodulação/fisiologia , Dor/fisiopatologia , Recidiva , Estresse Fisiológico/imunologiaRESUMO
The costimulatory CD40L-CD40 dyad plays a major role in multiple sclerosis (MS). CD40 is highly expressed on MHCII+ B cells, dendritic cells and macrophages in human MS lesions. Here we investigated the role of the CD40 downstream signaling intermediates TNF receptor-associated factor 2 (TRAF2) and TRAF6 in MHCII+ cells in experimental autoimmune encephalomyelitis (EAE). Both MHCII-CD40-Traf2-/- and MHCII-CD40-Traf6-/- mice showed a reduction in clinical signs of EAE and prevented demyelination. However, only MHCII-CD40-Traf6-/- mice displayed a decrease in myeloid and lymphoid cell infiltration into the CNS that was accompanied by reduced levels of TNF-α, IL-6 and IFN-γ. As CD40-TRAF6 interactions predominantly occur in macrophages, we subjected CD40flfl LysMcre mice to EAE. This myeloid-specific deletion of CD40 resulted in a significant reduction in EAE severity, reduced CNS inflammation and demyelination. In conclusion, the CD40-TRAF6 signaling pathway in MHCII+ cells plays a key role in neuroinflammation and demyelination during EAE. Concomitant with the fact that CD40-TRAF6 interactions are predominant in macrophages, depletion of myeloid CD40 also reduces neuroinflammation. CD40-TRAF6 interactions thus represent a promising therapeutic target for MS. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Assuntos
Antígenos CD40/fisiologia , Encefalomielite Autoimune Experimental/imunologia , Macrófagos/imunologia , Transdução de Sinais/imunologia , Fator 6 Associado a Receptor de TNF/fisiologia , Animais , Autoanticorpos/metabolismo , Antígenos CD40/deficiência , Ligante de CD40/fisiologia , Citocinas/metabolismo , Feminino , Imunoglobulina G/imunologia , Camundongos Endogâmicos C57BL , Esclerose Múltipla/imunologia , Glicoproteína Mielina-Oligodendrócito/imunologia , Neurite (Inflamação)/imunologiaRESUMO
Bifenthrin (BF) is a synthetic pyrethroid pesticide widely used in several countries to manage insect pests on diverse agricultural crops. Growing evidence indicates that BF exposure is associated with an increased risk of developing neurodegenerative disorders. However, the mechanisms by which BF induces neurological and anxiety alterations in the frontal cortex and striatum are not well known. The present in vivo study was carried out to determine whether reactive oxygen species (ROS)-mediated oxidative stress (OS) and neuroinflammation are involved in such alterations. Thirty-six Wistar rats were thus randomly divided into three groups and were orally administered with BF (0.6 and 2.1â¯mg/kg body weight, respectively) or the vehicle (corn oil), on a daily basis for 60 days. Results revealed that BF exposure in rats enhanced anxiety-like behavior after 60 days of treatment, as assessed with the elevated plus-maze test by decreases in the percentage of time spent in open arms and frequency of entries into these arms. BF-treated rats also exhibited increased oxidation of lipids and carbonylated proteins in the frontal cortex and striatum, and decreased glutathione levels and antioxidant enzyme activities including superoxide dismutase, catalase and glutathione peroxidase. Treatment with BF also increased protein synthesis and mRNA expression of the inflammatory mediators cyclooxygenase-2 (COX-2), microsomal prostaglandin synthase-1 (mPGES-1) and nuclear factor-kappaBp65 (NF-kBp65), as well as the production of tumor necrosis factor-α (TNF-α) and ROS. Moreover, BF exposure significantly decreased protein synthesis and mRNA expression of nuclear factor erythroid-2 (Nrf2) and acetylcholinesterase (AChE), as well as gene expression of muscarinic-cholinergic receptors (mAchR) and choline acetyltransferase (ChAT) in the frontal cortex and striatum. These data suggest that BF induced neurological alterations in the frontal cortex and striatum of rats, and that this may be associated with neuroinflammation and oxidative stress via the activation of Nrf2/NF-kBp65 pathways, which might promote anxiety-like behavior.
Assuntos
Ansiedade/etiologia , Inseticidas/toxicidade , Neurite (Inflamação)/induzido quimicamente , Síndromes Neurotóxicas/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Piretrinas/toxicidade , Tremor/etiologia , Animais , Comportamento Animal/efeitos dos fármacos , Biomarcadores/metabolismo , Neurônios Colinérgicos/efeitos dos fármacos , Neurônios Colinérgicos/imunologia , Neurônios Colinérgicos/metabolismo , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/imunologia , Corpo Estriado/metabolismo , Relação Dose-Resposta a Droga , Comportamento Exploratório/efeitos dos fármacos , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/imunologia , Lobo Frontal/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Inseticidas/administração & dosagem , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Proteínas do Tecido Nervoso/agonistas , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurite (Inflamação)/imunologia , Neurite (Inflamação)/metabolismo , Neurite (Inflamação)/fisiopatologia , Síndromes Neurotóxicas/imunologia , Síndromes Neurotóxicas/metabolismo , Piretrinas/administração & dosagem , Distribuição Aleatória , Ratos WistarRESUMO
In this approach, pre-stained cells from extrasanguinous fluids (ESFs) are stimulated in the presence of blood from the same individual. Thus, blood-derived antigen-presenting cells enable stimulation of both ESF- and blood T cells. Pre-staining allows distinction of T cells from ESF and blood, and simultaneous analysis of antigen-specific T cells in both compartments.
Assuntos
Células Apresentadoras de Antígenos/imunologia , Antígenos/imunologia , Herpesvirus Humano 3/imunologia , Imunoensaio/métodos , Meningite Viral/diagnóstico , Linfócitos T/imunologia , Adulto , Líquido Cefalorraquidiano/citologia , Humanos , Meningite Viral/imunologia , Meningite Viral/virologia , Mycobacterium tuberculosis/imunologia , Neurite (Inflamação)/imunologia , Neurite (Inflamação)/virologia , Recidiva , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/imunologiaRESUMO
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease leading to paralysis and death within 3-5 years of its diagnosis. The SOD1G93A mouse is used extensively as an ALS animal model. Increasing evidence shows that non-neuronal cellscontribute to the pathogenesis and progression of ALS. Among them, many studies focus on microgliosis in the spinal cord (SC); while few on macrophage activation in the sciatic nerves. Substantial evidence shows that insulin-like growth factor 1 (IGF1) delays disease progression and increases the lifespan of SOD1G93A mice, and some studies indicate that IGF1 reduces inflammation in the SC of ALS mice. However, no studies have focused on the effect of IGF on sciatic nerve inflammation. Here, we find that ALS progression is characterized by increasing macrophage invasion and activation accompanied by significant TNF-α production in the sciatic nerve. Furthermore, IGF1 treatment and knockdown alleviate and aggravate these responses, respectively. Collectively, our findings show the first time that IGF1 has an anti-inflammatory effect in the sciatic nerves of SOD1G93A mice.
Assuntos
Esclerose Lateral Amiotrófica , Fator de Crescimento Insulin-Like I/farmacologia , Macrófagos/efeitos dos fármacos , Neurite (Inflamação) , Nervo Isquiático , Fator de Necrose Tumoral alfa/metabolismo , Esclerose Lateral Amiotrófica/tratamento farmacológico , Esclerose Lateral Amiotrófica/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Fator de Crescimento Insulin-Like I/deficiência , Camundongos , Camundongos Knockout , Neurite (Inflamação)/tratamento farmacológico , Neurite (Inflamação)/imunologia , Neurite (Inflamação)/metabolismo , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/imunologia , Nervo Isquiático/metabolismo , Superóxido Dismutase-1/genéticaRESUMO
Aluminum (Al) is a neurotoxic associated with a number of chronic human diseases. We investigated the effects of Al exposure at doses similar to human dietary levels and at a high level exposure to Al on the peripheral nervous system. Wistar male rats were divided into two major groups and received orally: 1) First group - Low level - rats were subdivided and treated for 60days: a) Control - received ultrapure water; b) AlCl3 - received Al at 8.3mg/kg body weight (bw) for 60days; and 2) Second group - High level - rats were subdivided and treated for 42days: C) Control - received ultrapure water through oral gavage; d) AlCl3 - received Al at 100mg/kg bw for 42days. Von Frey hair test, plantar test, the presence of catalepsy and the spontaneous motor activity were investigated. Reactive oxygen species, lipid peroxidation and total antioxidant capacity, immunohistochemistry to investigate the nerve inflammation and, the specific presence of Al in the sciatic nerve fibers were investigated. Al exposure at a representative human dietary level promotes the development of mechanical allodynia, catalepsy, increased inflammation in the sciatic nerve, systemic oxidative stress and, is able to be retained in the sciatic nerve. The effects of low-dose Al were similar to those found in rats exposed to Al at a dose much higher (100mg/kg). Our findings suggest that Al may be considered toxic for the peripheral nervous system, thus inducing peripheral dysfunction.
Assuntos
Alumínio/toxicidade , Neurite (Inflamação)/etiologia , Síndromes Neurotóxicas/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Doenças do Sistema Nervoso Periférico/etiologia , Sistema Nervoso Periférico/efeitos dos fármacos , Poluentes da Água/toxicidade , Alumínio/administração & dosagem , Animais , Comportamento Animal/efeitos dos fármacos , Catalepsia/etiologia , Relação Dose-Resposta a Droga , Hiperalgesia/etiologia , Peroxidação de Lipídeos/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Masculino , Neurite (Inflamação)/imunologia , Neurite (Inflamação)/metabolismo , Neurite (Inflamação)/fisiopatologia , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/patologia , Sistema Nervoso Periférico/imunologia , Sistema Nervoso Periférico/fisiopatologia , Doenças do Sistema Nervoso Periférico/imunologia , Doenças do Sistema Nervoso Periférico/metabolismo , Doenças do Sistema Nervoso Periférico/fisiopatologia , Ratos Wistar , Espécies Reativas de Oxigênio/sangue , Espécies Reativas de Oxigênio/metabolismo , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/imunologia , Nervo Isquiático/metabolismo , Nervo Isquiático/patologia , Fatores de Tempo , Distribuição Tecidual , Testes de Toxicidade Crônica , Toxicocinética , Poluentes da Água/administração & dosagemRESUMO
Background: Leprosy is a complex infectious and neurological disease caused by Mycobacterium leprae. Nerve damage is related to immunological hypersensitivity responses known as leprosy reactions (LRs). Diagnostic tools to predict LRs are not available. We hypothesized that natural octyl disaccharide-leprosy IDRI diagnostic (NDO-LID) would be helpful as an indicator of LRs and neuritis. Methods: To assess the utility of NDO-LID in indicating reactions, ELISA were used to detect specific antibodies in serum samples from 80 Colombian leprosy patients (40 with and 40 without history of LRs). Responses were detected using a range of detection reagents detecting IgG, IgM or both isotypes. Results: Patients with a history of LRs had an increased seropositivity rate for anti-NDO-LID antibodies compared to patients without (anti-NDO-LID protein A [p=0.02], IgG anti-NDO-LID [p=0.01] and IgM anti-NDO-LID [p=0.01]). Further analyses of patients with a history of LRs indicated that both seropositivity rate and magnitude of responses were elevated among patients with neuritis versus those without neuritis (anti-NDO-LID protein A [p=0.03], IgG anti-NDO-LID [p=0.001] and IgM anti-NDO-LID [p=0.06]). Conclusions: Our data indicate that testing for serum anti-NDO-LID antibodies can be a useful screen to identify patients at risk of developing LRs and neuritis.
Assuntos
Anticorpos Antibacterianos/sangue , Hanseníase/sangue , Mycobacterium leprae/enzimologia , Neurite (Inflamação)/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Colômbia , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G , Imunoglobulina M , Hanseníase/imunologia , Hanseníase/fisiopatologia , Masculino , Pessoa de Meia-Idade , Mycobacterium leprae/imunologia , Neurite (Inflamação)/imunologia , Neurite (Inflamação)/fisiopatologia , Valor Preditivo dos Testes , Testes Sorológicos , Adulto JovemRESUMO
Geraniol (GER) is a monoterpene alcohol with various biochemical and pharmacological properties present in the essential oil of more than 160 species of herbs (especially the Cymbopogon genus). In this study, we evaluated the antinociceptive activity of GER in behavioural and electrophysiological in vitro experimental models of nociception using male Swiss mice. GER (12.5, 25 or 50 mg/kg i.p. and 50 or 200 mg/kg p.o.) reduced the number of writhes induced by acetic acid. The opioid antagonist naloxone (5 mg/kg s.c.) administered in mice subsequently treated with GER (25 mg/kg i.p.) did not reverse such antinociceptive activity, suggesting a non-opioid pathway for the mechanism of action. GER (12.5, 25 and 50 mg/kg i.p.) reduced paw licking time in the second phase of the formalin test. Also, in the glutamate test, GER when administered 50 mg/kg i.p. reduced paw licking time, probably modulating glutamatergic neurotransmission. GER blocked reversibly components of the compound action potential (CAP) recorded in isolated sciatic nerve in a concentration- and drug exposure time-dependent manner: 1 mM to 120 min. for the first component and 0.6 mM to 90 min. for the second component. The IC50 was calculated for the peak-to-peak amplitude (PPA) at 0.48 ± 0.04 mM. The conduction velocity was also reduced by exposure to GER starting from the concentration of 0.3 mM for both components of the CAP. In conclusion, it is suggested that GER has antinociceptive activity, especially in pain related to inflammation, and in part related to reduced peripheral nerve excitability.
Assuntos
Analgésicos/uso terapêutico , Modelos Animais de Doenças , Modelos Neurológicos , Neurite (Inflamação)/tratamento farmacológico , Neurônios/efeitos dos fármacos , Nervo Isquiático/efeitos dos fármacos , Terpenos/uso terapêutico , Potenciais de Ação/efeitos dos fármacos , Monoterpenos Acíclicos , Administração Oral , Analgésicos/administração & dosagem , Analgésicos/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Técnicas In Vitro , Injeções Intraperitoneais , Cinética , Masculino , Camundongos , Condução Nervosa/efeitos dos fármacos , Neurite (Inflamação)/imunologia , Neurônios/imunologia , Nervo Isquiático/fisiologia , Transmissão Sináptica/efeitos dos fármacos , Terpenos/administração & dosagem , Terpenos/farmacologiaRESUMO
IgG4-related disease (IgG4-RD) is a chronic inflammatory disorder, characterized by elevated serum IgG4 levels as well as abundant infiltration of IgG4-positive plasmacytes and fibrosis in various organs, including the head and neck region. In particular, the salivary glands, orbit, and thyroid are common sites of disease involvement. IgG4-RD is diagnosed based on various clinical, serological, and histopathological findings, none of which are pathognomonic. Hence, various differential diagnoses, which exhibit elevated serum IgG4 levels and infiltration of IgG4-postive cells into tissues, need to be excluded, especially malignant diseases and mimicking disorders. Systemic corticosteroids are generally effective in inducing IgG4-RD remission; however, recurrent or refractory cases are common. In addition, although the pathogenic mechanisms of IgG4-RD remain unclear, an antigen-driven inflammatory condition is believed to be involved. Recent studies have indicated the important pathogenic role of B cell/T cell collaboration and innate immunity in this disease. Nevertheless, additional research and discussions are needed to resolve many remaining questions. In this review, we provide an overview of the recent insights on the history, clinical features, diagnosis, and treatment of IgG4-RD in the head and neck region. Furthermore, we have also addressed the pathogenesis of this disease.
Assuntos
Doenças Autoimunes/imunologia , Dacriocistite/imunologia , Imunoglobulina G/imunologia , Rinite/imunologia , Sialadenite/imunologia , Sinusite/imunologia , Tireoidite Autoimune/imunologia , Corticosteroides/uso terapêutico , Doenças Autoimunes/tratamento farmacológico , Hipofisite Autoimune/tratamento farmacológico , Hipofisite Autoimune/imunologia , Dacriocistite/tratamento farmacológico , Humanos , Linfadenite/tratamento farmacológico , Linfadenite/imunologia , Mastoidite/tratamento farmacológico , Mastoidite/imunologia , Neurite (Inflamação)/tratamento farmacológico , Neurite (Inflamação)/imunologia , Otite/tratamento farmacológico , Otite/imunologia , Rinite/tratamento farmacológico , Sialadenite/tratamento farmacológico , Sinusite/tratamento farmacológico , Tireoidite Autoimune/tratamento farmacológicoRESUMO
In the era of highly active antiretroviral therapy (HAART), HIV-1-associated neurocognitive disorders (HAND) persist in infected individuals with adequate immunological and virological status. Risk factors for cognitive impairment include hepatitis C virus co-infection, host genetic factors predisposing to HAND, the early establishment of the virus in the CNS and its persistence under HAART; thus, the CNS is an important reservoir for HIV. Microglial cells are permissive to HIV-1, and NLRP3 inflammasome-associated genes were found expressed in brains of HIV-1-infected persons, contributing to brain disease. Inflammasomes can be triggered by alarmins or danger-associated molecular patterns (DAMPs), which directly stimulate the production of proinflammatory mediators by glial cells, contribute to blood-brain barrier injury through induction of release of various proteases and allow the passage of infected macrophages, and trigger IL-1ß release from primed cells. Amongst alarmins involved in HIV-1-induced neuropathogenesis, IL-33 and high-mobility group box 1 (HMGB1) are of particular interest. Neurocognitive alterations were recently associated with dysregulation of the IL-33/ST2 axis in the CNS, leading to the induction of neuronal apoptosis, decrease in synaptic function and neuroinflammation. Specific biomarkers, including HMGB1 and anti-HMGB1 antibodies, have been identified in cerebrospinal fluid from patients with HAND, correlated with immune activation and identifying a very early stage of neurocognitive impairment that precedes changes in metabolites detected by magnetic resonance spectroscopy. Moreover, HMGB1 plays a crucial role in HIV-1 persistence in dendritic cells and in the constitution of viral reservoirs. In this review, the mechanisms whereby alarmins contribute to HIV-1-induced CNS inflammation and neuropathogenesis will be discussed.
Assuntos
Alarminas/fisiologia , Doenças do Sistema Nervoso Central/virologia , Infecções por HIV/etiologia , HIV-1 , Neurite (Inflamação)/virologia , Fármacos Anti-HIV/uso terapêutico , Biomarcadores/metabolismo , Doenças do Sistema Nervoso Central/imunologia , Doença Crônica , Reservatórios de Doenças , Proteína gp120 do Envelope de HIV/fisiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Proteína HMGB1/fisiologia , Humanos , Imunidade Inata/imunologia , Inflamassomos/fisiologia , Interleucina-33/fisiologia , Neurite (Inflamação)/imunologia , Doenças Neurodegenerativas/imunologia , Doenças Neurodegenerativas/virologia , Produtos do Gene tat do Vírus da Imunodeficiência Humana/fisiologiaRESUMO
BACKGROUND: Leprosy reactions are immunologically mediated conditions and a major cause of disability before, during and after multidrug therapy (MDT). Little data have been published on the epidemiology of leprosy reactions in Bangladesh. OBJECTIVES: To describe the pattern and prevalence of leprosy reactions in the postelimination stage. METHODS: A descriptive retrospective cross-sectional study was carried out in Chittagong Medical College Hospital using the registered records of patients in the period between 2004 and 2013. RESULTS: Of the 670 patients with leprosy, 488 (73.38%) were males and 182 (27.37%) were females. The prevalence of reaction was in 300 (44.78%) patients with a male:female ratio of 3.55 : 1. The age-specific cumulative reaction cases at >40 years were 115 (38.33%) among all age groups. The prevalence of reaction was found to be in 166 (55.33%) patients for the reversal reaction, 49 (16.57%) for the erythema nodosum leprosum (ENL) and 85 (28.33%) for the neuritis. Borderline tuberculoid was most common (106, 35.33%)in the reversal reaction group, while lepromatous leprosy was most common (37, 12.33%) in ENL group. More than half of the patients (169, 56.33%) had reactions at the time of presentations, while 85 (28.33%) and 46 (15.33%) patients developed reaction during and after MDT, respectively. The reversal reaction group presented with ≥six skin lesions in 96 (57.83%) patients and ≥two nerve function impairments (NFIs) in 107 (64.46%) patients. The ENL was present chiefly as papulo-nodular lesions in 45 (91.84%) patients followed by pustule-necrotic lesions in four (8.16%), neuritis in 33 (67.35%), fever in 24 (48.98%), lymphadenitis in six (12.24%), arthritis in five (10.20%) and iritis in two (4.08%). Bacterial index ≥3 had been demonstrated in 34 (60.71%) patients in ENL group. CONCLUSION: The incidence of leprosy reaction seemed to be more than three times common in borderline tuberculoid (52.33%) group than in lepromatous leprosy (14%) group. Reactions with NFI and disability still occur among multibacillary patients during and after MDT. Early detection and management of leprosy reaction are very important in preventing disability and deformity, and patients should be educated to undergo regular follow-up examinations. Developing reinforced new therapies to curb leprosy reactions is crucial for improving leprosy healthcare services.
Assuntos
Eritema Nodoso/imunologia , Hipersensibilidade Tardia/complicações , Hipersensibilidade Tardia/epidemiologia , Hanseníase/tratamento farmacológico , Linfadenite/imunologia , Neurite (Inflamação)/imunologia , Adolescente , Adulto , Antígenos de Bactérias/imunologia , Artrite/epidemiologia , Artrite/imunologia , Bangladesh/epidemiologia , Criança , Pré-Escolar , Eritema Nodoso/epidemiologia , Feminino , Humanos , Lactente , Irite/epidemiologia , Irite/imunologia , Hansenostáticos/uso terapêutico , Hanseníase Dimorfa/tratamento farmacológico , Hanseníase Virchowiana/tratamento farmacológico , Hanseníase Tuberculoide/tratamento farmacológico , Linfadenite/epidemiologia , Masculino , Neurite (Inflamação)/epidemiologia , Prevalência , Estudos Retrospectivos , Adulto JovemAssuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Encéfalo/diagnóstico por imagem , Glicoproteína Mielina-Oligodendrócito/imunologia , Neurite (Inflamação)/etiologia , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Encefalite Antirreceptor de N-Metil-D-Aspartato/imunologia , Criança , Eletroencefalografia , Feminino , Humanos , Imageamento por Ressonância Magnética , Neurite (Inflamação)/diagnóstico , Neurite (Inflamação)/imunologiaRESUMO
Distinguishing between hereditary and inflammatory neuropathy is usually straightforward on clinical grounds with the help of a family history. There are nevertheless cases where the distinction is less clear. The advent of molecular genetics has in the past several years aided confirmatory diagnosis for an increasing proportion of patients with genetic neuropathy. Various reports have described associations of Charcot-Marie-Tooth disease with a suspected or confirmed inflammatory neuropathy occasionally responding to immunotherapy. Possible predisposition to an inflammatory component was suggested in a subset of patients. Such reports have, however, been relatively few in number, suggesting the rarity of such associations and of such a predisposition if it exists. There have been a number of publications detailing clinical presentations suggestive of inflammatory neuropathy in patients with a known or later proven genetic aetiology, and subsequently felt to be part of the phenotype rather than representing an association. A number of genetically mediated multisystemic diseases with neuropathy have otherwise been reported as mimicking chronic inflammatory demyelinating polyneuropathy (CIDP). The most common example is that of familial amyloid polyneuropathy, of particular concern for the clinician when misdiagnosed as CIDP, in view of the therapeutic implications. We review the literature on reported associations, mimics and misdiagnoses of hereditary and inflammatory neuropathy and attempt to determine a practical approach to the problem in clinical practice using clinical features, electrophysiology, histopathology and targeted early genetic testing. The issue of attempting immunomodulatory therapy is discussed in view of the published literature.
Assuntos
Neuropatia Hereditária Motora e Sensorial/diagnóstico , Neuropatia Hereditária Motora e Sensorial/genética , Neurite (Inflamação)/diagnóstico , Neurite (Inflamação)/genética , Doença de Charcot-Marie-Tooth/diagnóstico , Doença de Charcot-Marie-Tooth/genética , Doença de Charcot-Marie-Tooth/terapia , Erros de Diagnóstico , Predisposição Genética para Doença , Testes Genéticos , Humanos , Doenças do Sistema Nervoso , Neurite (Inflamação)/imunologia , FenótipoRESUMO
OBJECTIVE: Sesamin is known for its role in antioxidant, antiproliferative, antihypertensive, and neuroprotective activities. However, little is known about the role of sesamin in the development of emotional disorders. Here we investigated persistent inflammatory pain hypersensitivity and anxiety-like behaviors in the mouse suffering chronic pain. METHODS: Chronic inflammatory pain was induced by hind paw injection of complete Freund's adjuvant (CFA). Levels of protein were detected by Western blot. RESULTS: Administration of sesamin could induce anxiolytic activities but had no effect on analgesia. In the basolateral amygdala, a structure involving the anxiety development, sesamin attenuated the up-regulation of NR2B-containing N-methyl-d-aspartate receptors, GluR1 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor as well as phosphorylation of GluR1 at Ser831 (p-GluR1-Ser831), and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII-alpha) in the hind paw CFA-injected mice. In the same model, we found that the sesamin blocked the down-regulation of gamma-aminobutyric acid A (GABAA-alpha-2) receptors. CONCLUSION: Our findings show that sesamin reduces anxiety-like behaviors induced by chronic pain at least partially through regulating the GABAergic and glutamatergic transmission in the amygdala of mice.