RESUMO
There is increasing evidence that neurofilament light chain (NF-L) can be considered as a biomarker for neuro-axonal damage. This polypeptide can be released into the cerebrospinal fluid (CSF) and the blood, where it can be quantified. The concentration of NF-L is elevated in patients with multiple sclerosis (MS) and psychiatric disorders. We aimed to investigate the NF-L levels in the CSF from treated MS patients and the relationship with depression or anxiety. The study involved three groups: control group (individuals without inflammation), the relapse-remitting multiple sclerosis (RRMS)-untreated group, and the RRMS-Fingo group (RRMS patients who were treated with fingolimod). MS disability was assessed by the Expanded Disability Status Scale, and depression and anxiety were evaluated by a neuropsychologist, using the Hospital Anxiety and Depression Scale, the Beck Depression Inventory-II, and the Beck Anxiety Inventory. Individual CSF samples were collected to measure NF-L levels. The results of the statistical analysis on levels of NF-L in the CSF of control subjects, RRMS-untreated patients, and RRMS-Fingo patients were significant. The relationship between depression and anxiety in RRMS-Fingo patients and NF-L levels was not statistically significant. In conclusion, MS events such as anxiety and depression appear to contribute to the onset of clinical relapses, subclinical cases, and neurodegeneration.
Assuntos
Transtornos de Ansiedade , Depressão , Esclerose Múltipla , Transtornos de Ansiedade/etiologia , Biomarcadores , Depressão/etiologia , Humanos , Filamentos Intermediários , Esclerose Múltipla/complicações , Proteínas de NeurofilamentosRESUMO
There is increasing evidence that neurofilament light chain (NF-L) can be considered as a biomarker for neuro-axonal damage. This polypeptide can be released into the cerebrospinal fluid (CSF) and the blood, where it can be quantified. The concentration of NF-L is elevated in patients with multiple sclerosis (MS) and psychiatric disorders. We aimed to investigate the NF-L levels in the CSF from treated MS patients and the relationship with depression or anxiety. The study involved three groups: control group (individuals without inflammation), the relapse-remitting multiple sclerosis (RRMS)-untreated group, and the RRMS-Fingo group (RRMS patients who were treated with fingolimod). MS disability was assessed by the Expanded Disability Status Scale, and depression and anxiety were evaluated by a neuropsychologist, using the Hospital Anxiety and Depression Scale, the Beck Depression Inventory-II, and the Beck Anxiety Inventory. Individual CSF samples were collected to measure NF-L levels. The results of the statistical analysis on levels of NF-L in the CSF of control subjects, RRMS-untreated patients, and RRMS-Fingo patients were significant. The relationship between depression and anxiety in RRMS-Fingo patients and NF-L levels was not statistically significant. In conclusion, MS events such as anxiety and depression appear to contribute to the onset of clinical relapses, subclinical cases, and neurodegeneration.
Assuntos
Humanos , Transtornos de Ansiedade/etiologia , Depressão/etiologia , Esclerose Múltipla/complicações , Filamentos Intermediários , Biomarcadores , Proteínas de NeurofilamentosRESUMO
It has been shown that administration of TNF-alpha causes an increase of survival of plasmodium-infected mice. However, this anti-parasitic effect cannot be reproduced in vitro upon direct incubation of the cytokine with the parasite. This suggests that TNF-alpha may act through modulation of some plasmodicidal mechanism not yet clarified. We evaluated the effect of exogenous TNF-alpha on the phagocytosis of Plasmodium falciparum-infected erythrocytes by monocytes and its influence on the ability of monocytes and lymphocytes to inhibit parasite growth. The capacity of endogenous TNF-alpha to influence the ability of monocytes to inhibit the parasite was also verified. We found that addition of 33 ng TNF-alpha/mL to cultures of human monocytes and P. falciparum-infected erythrocytes increased the phagocytic index from 3.8 to 7.8 in the presence of serum containing P. falciparum antibody. TNF-alpha increased the capacity of monocyte plus lymphocyte to inhibit parasite growth by about 3 times at 0.5 and 5 ng/mL. Sera from severely ill P. falciparum-infected individuals inhibited the parasite growth, but addition of anti-TNF-alpha antibody was unable to modify this inhibition. These data show that TNF-alpha can increase the phagocytic capacity. This was probably due to an increased expression of Fc receptors on monocytes or to the modulation of Fc receptor signaling pathways by signals originating from the binding of TNF-alpha to its receptors. TNF-alpha also acted on lymphocytes plus monocytes by increasing the inhibition of P. falciparum by a mechanism not related to phagocytosis. These findings suggest that TNF-alpha has a pleiotropic anti-malaria effect and that this protective effect depends on the interplay of different factors, such as monocytes/macrophages, lymphocytes, and antibodies, in addition to other cells and molecules.
Assuntos
Eritrócitos/imunologia , Linfócitos/imunologia , Monócitos/imunologia , Fagocitose/imunologia , Plasmodium falciparum/imunologia , Fator de Necrose Tumoral alfa/imunologia , Adulto , Animais , Anticorpos Antiprotozoários/imunologia , Técnicas de Cocultura , Eritrócitos/efeitos dos fármacos , Eritrócitos/parasitologia , Humanos , Linfócitos/efeitos dos fármacos , Malária Falciparum/sangue , Malária Falciparum/imunologia , Monócitos/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Plasmodium falciparum/crescimento & desenvolvimento , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
A 23 year-old man with prolonged fever caused by Brucella abortus is reported. The uncommon feature of this case was the presence of a spleen abscess identified by computer tomography of the abdomen. Patient evolution was favorable after treatment with antibiotics, with complete regression of the lesions.
Assuntos
Abscesso Abdominal/microbiologia , Brucelose/patologia , Esplenopatias/microbiologia , Abscesso Abdominal/patologia , Adulto , Brucella abortus , Humanos , Masculino , Radiografia Abdominal , Esplenopatias/patologia , Tomografia Computadorizada por Raios XRESUMO
A critical role has been proposed for the switch from non-cytophilic IgG2 to cytophilic antibodies of IgG1 and IgG3 subclasses observed in the humoral immune responses to Plasmodium falciparum of some Africans. These Africans have acquired clinically immunity naturally, after several years of exposure to holo-endemic malaria. In the present study, the possibility that life-long exposure to low levels of malarial endemicity may be associated with changes in the IgG-subclass composition of antibodies to P. falciparum was investigated in a native Amazonian community. The subjects were 138 malaria-exposed but non-infected Karitiana Indians. In a separate investigation, the concentrations of IgG-subclass antibodies in acutely ill patients with severe malaria (N = 22) were compared with those in age- and sex-matched controls who had uncomplicated malaria (N = 44). Plasma concentrations of IgG against a detergent-soluble extract of P. falciparum schizonts were measured by quantitative ELISA, using indirect standardization. Among the Karitiana, the concentrations of anti-parasite antibodies of all subclasses increased with age, and there was no correlation between age and the proportion of such antibodies which was cytophilic. The predominance of cytophilic IgG1 and non-cytophilic IgG2 antibodies in all age-groups of the Karitiana provides an example of an intermediate pattern of immune responses to P. falciparum which contrasts with those previously described in both clinically immune and non-immune populations. Although mean concentrations of cytophilic IgG1 against P. falciparum were significantly higher in the controls than in the patients with severe malaria, there were no significant differences in other IgG subclasses. Lack of exposure to malaria in the past was associated with disease severity (odds ratio = 4.75; 95% confidence interval = 1.31-17.42), and may explain, at least partially, the occurrence of defective, low-IgG1 antibody responses to P. falciparum in those subjects who had severe malaria.
Assuntos
Anticorpos Antiprotozoários/sangue , Imunoglobulina G/sangue , Malária Falciparum/imunologia , Plasmodium falciparum/imunologia , Doença Aguda , Adolescente , Adulto , Idoso , Envelhecimento/imunologia , Animais , Brasil , Criança , Pré-Escolar , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Indígenas Sul-Americanos , Lactente , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
The dysregulation of the immune response by malaria parasite has been considered as a possible constraint to the effectiveness of malaria vaccination. In spite of the important role interleukin-1 (IL-1) plays on the immunoregulation, and its ability to mimic various features of clinical malaria, reports on IL-1 in malaria are lacking. We found that only 2 out of 35 subjects with acute malaria showed increased levels of serum IL-1 alpha by enzyme immunoassay. To assess whether IL-1 could interfere with T-lymphocyte responses, blood mononuclear cells from patients infected with Plasmodium falciparum, P. vivax, or healthy subjects were cultured with phytohemagglutinin, and lymphocyte proliferation measured 72 h later by 3H-thymidine incorporation. Our data showed that T-lymphocyte responses are depressed both in P. falciparum (10,500 +/- 2,900) and P. vivax malaria (13,000 +/- 3,300), as compared to that of healthy individuals (27,000 +/- 3,000). Addition of IL-1 partially reversed depression of malaria lymphocytes, but had no effect on normal cells. On the other hand, T-lymphocytes from malaria infected-subjects presented a minimal decrease in proliferation, when cultured in the presence of exogenous PGE2. These data indicate the occurrence of two defects of immunoregulation in malaria: a deficiency of IL-1 production by monocytes/macrophages, and an increased resistance of lymphocytes to the antiproliferative effect of PGE2.