RESUMO
Neuropeptide Y (NPY), a major autonomic nervous system and stress mediator, is emerging as an important regulator of inflammation, implicated in autoimmunity, asthma, atherosclerosis, and cancer. Yet the role of NPY in regulating phenotype and functions of dendritic cells (DCs), the professional antigen-presenting cells, remains undefined. Here we investigated whether NPY could induce DCs to migrate, mature, and polarize naive T lymphocytes. We found that NPY induced a dose-dependent migration of human monocyte-derived immature DCs through the engagement of NPY Y1 receptor and the activation of ERK and p38 mitogen-activated protein kinases. NPY promoted DC adhesion to endothelial cells and transendothelial migration. It failed to induce phenotypic DC maturation, whereas it conferred a T helper 2 (Th2) polarizing profile to DCs through the up-regulation of interleukin (IL)-6 and IL-10 production. Thus, during an immune/inflammatory response NPY may exert proinflammatory effects through the recruitment of immature DCs, but it may exert antiinflammatory effects by promoting a Th2 polarization. Locally, at inflammatory sites, cell recruitment could be amplified in conditions of intense acute, chronic, or cold stress. Thus, altered or amplified signaling through the NPY-NPY-Y1 receptor-DC axis may have implications for the development of inflammatory conditions.-Buttari, B., Profumo, E., Domenici, G., Tagliani, A., Ippoliti, F., Bonini, S., Businaro, R., Elenkov, I., Riganò, R. Neuropeptide Y induces potent migration of human immature dendritic cells and promotes a Th2 polarization.
Assuntos
Movimento Celular/fisiologia , Células Dendríticas/fisiologia , Neuropeptídeo Y/metabolismo , Células Th2/fisiologia , Adesão Celular/fisiologia , Proliferação de Células , Células Cultivadas , Células Dendríticas/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/fisiologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Inflamação/metabolismo , Inflamação/fisiopatologia , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Receptores de Neuropeptídeo Y , Células Th2/metabolismo , Migração Transendotelial e Transepitelial/fisiologia , Regulação para Cima/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
INTRODUCTION: Man devotes most of the daily time to work, and also a large part of physical and mental resources. Depression and many other morbid conditions can be related etiopathologically to the performance of a dangerous occupation in terms of quality (hazardous work activities, lack of motivation for deficient career opportunities) or merely quantitative (duration of work shifts, frequency shifts work). The medical legal ascertainment is limited because stress cannot be valued by objective nature, but only through precious elements collected directly by workers by questionnaires. This is in response to legal requirements in terms of civil liability, occupational disease and disability. AIM AND METHODS: The objective of this study is to analyze the change of cytokines (IL-6, IL-12, TNF-α) and stress-related hormones (prolactin and cortisol) in a sample of 314 individuals working at the University Hospital Umberto I in Rome without acute diseases but only with the "feeling stressed" for at least a month and to analyze if there is a correlation between some of these biochemical variables and stress values measured by questionnaire. RESULTS: The results of this study confirm the usefulness to associate laboratory analysis, such as the study of inflammatory cytokines and the hormonal profile, to psychometric tests, precious for the lower cost and in some cases also for the high diagnostic sensitivity, to reach a probative value which satisfies even the most demanding application of accuracy.
Assuntos
Doenças Profissionais/sangue , Estresse Psicológico/sangue , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Hidrocortisona/sangue , Interleucina-12/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/diagnóstico , Saúde Ocupacional/legislação & jurisprudência , Prolactina/sangue , Estresse Psicológico/diagnóstico , Fator de Necrose Tumoral alfa/sangueRESUMO
Obesity is now growing at an alarming rate reaching epidemic proportions worldwide thus increasing morbidity and mortality rates for chronic disease. But although we have ample information on the complications associated with obesity, precisely what causes obesity remains poorly understood. Some evidence attributes a major role to a low-grade chronic inflammatory state (neurogenic inflammation) induced in obesity by inflammatory mediators produced and secreted within the expanded activated adipocyte pool. Adipose tissue is an endocrine organ that secretes numerous adipose tissue-specific or enriched hormones, known as adipokines, cytokine-like molecules thought to play a pathogenic role in cardiovascular diseases. The imbalance between increased inflammatory stimuli and decreased anti-inflammatory mechanisms may depend on chronic stress. Hence the positive correlation found between stress, obesity and cardiovascular diseases. The chronic inflammatory state associated with insulin resistance and endothelial dysfunction is highly deleterious for vascular function. This review focuses on the proposed neuroimmunodulatory mechanisms linking chronic (psychological) stress, obesity and cardiovascular diseases.
Assuntos
Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/patologia , Neuroimunomodulação/fisiologia , Obesidade/imunologia , Obesidade/patologia , Estresse Psicológico/imunologia , Estresse Psicológico/patologia , Alostase/fisiologia , Doenças Cardiovasculares/epidemiologia , Comorbidade , Matriz Extracelular/fisiologia , Humanos , Inflamação/imunologia , Inflamação/patologia , Inflamação/fisiopatologia , Leptina/fisiologia , Macrófagos/imunologia , Macrófagos/fisiologia , Obesidade/epidemiologia , Fatores de RiscoRESUMO
Atherosclerosis initiation and progression is controlled by inflammatory molecular and cellular mediators. Cells of innate immunity, stimulated by various endogenous molecules that have undergone a transformation following an oxidative stress or nonenzymatic glycation processes, activate cells of the adaptive immunity, found at the borders of atheromas. In this way, an immune response against endogenous modified antigens takes place and gives rise to chronic low-level inflammation leading to the slow development of complex atherosclerotic plaques. These lesions will occasionally ulcerate, thus ending with fatal clinical events. Plaque macrophages represent the majority of leukocytes in the atherosclerotic lesions, and their secretory activity, including proinflammatory cytokines and matrix-degrading proteases, may be related to the fragilization of the fibrous cap and then to the rupture of the plaque. A considerable amount of work is currently focused on the identification of locally released proinflammatory factors that influence the evolution of the plaque to an unstable phenotype. A better understanding of these molecular processes may contribute to new treatment strategies. Mediators released by the immune system and associated with the development of carotid atherosclerosis are discussed.
Assuntos
Placa Aterosclerótica/etiologia , Imunidade Adaptativa , Animais , Autoantígenos/metabolismo , Doenças das Artérias Carótidas/etiologia , Doenças das Artérias Carótidas/imunologia , Doenças das Artérias Carótidas/patologia , Citocinas/imunologia , Progressão da Doença , Proteínas de Choque Térmico/imunologia , Hemoglobinas/imunologia , Humanos , Imunidade Inata , Mediadores da Inflamação/imunologia , Macrófagos/imunologia , Placa Aterosclerótica/imunologia , Placa Aterosclerótica/patologia , Subpopulações de Linfócitos T/imunologia , beta 2-Glicoproteína I/imunologiaRESUMO
The incidence of AD is increasing in parallel with the increase in life expectancy. At the same time the prevalence of metabolic syndrome and obesity is reaching epidemic proportions in western populations. Stress is one of the major inducers of visceral fat and obesity development, underlying accelerated aging processes. Adipose tissue is at present considered as an active endocrine organ, producing important mediators involved in metabolism regulation as well as in inflammatory mechanisms. Insulin and leptin resistance has been related to the dysregulation of energy balance and to the induction of a chronic inflammatory status which have been recognized as important cofactors in cognitive impairment and AD initiation and progression. The aim of this paper is to disclose the correlation between the onset and progression of AD and the stress-induced changes in lifestyle, leading to overnutrition and reduced physical activity, ending with metabolic syndrome and obesity. The involved molecular mechanisms will be briefly discussed, and advisable guide lines for the prevention of AD through lifestyle modifications will be proposed.
RESUMO
Increasing evidence has been accumulating about the role of stress as an important challenge to the onset and progression of Alzheimer's disease (AD). The hippocampus, one of the areas of the brain damaged during AD, was the first brain region, besides the hypothalamus, to be recognized as a target of stress hormones, including cortisol, sympathetic and parasympathetic transmitters, cytokines, and metabolic hormones. The present review aims at summarizing neuroinflammatory mechanisms induced by stress, resulting in neuronal dysfunction and impaired neurogenesis. Lifestyle and environmental factors related to metabolic and inflammatory alterations observed in stressed subjects and thought to favor AD development and progression, as well as the possible ways of prevention, are discussed.
Assuntos
Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Citocinas/metabolismo , Neurônios/metabolismo , Estresse Oxidativo/fisiologia , Estresse Psicológico/metabolismo , Doença de Alzheimer/psicologia , Animais , Humanos , Mediadores da Inflamação/metabolismoRESUMO
OBJECTIVE: Despite emerging evidence suggesting a link between alexithymia and immune function, previous studies yielded contrasting results. The proposed link between alexithymia and immune function remains controversial as does the role, in this relationship, of anxiety, depression and subjective stress. The aim of the study is to investigate the possible association between alexithymia and circulating levels of cytokines in subjects awaiting an upper endoscopy, a stressful procedure, controlling for anxiety levels, depression and subjective stress. METHODS: Participants were recruited from among consecutive patients referred for routine diagnostic upper endoscopy. All participants completed the Toronto Alexithymia Scale (TAS-20), the Hospital Anxiety and Depression Scale, and the Stress-related Vulnerability Scale. Serum levels of IL-1ß, IL-4, IL-6, IL-10, TNF-α and IFN-γ were measured by ELISA. RESULTS: Of the 90 subjects initially approached, 68 completed the study. The TAS-20 identified 22 alexithymic and 36 non-alexithymic patients. ELISA detected significantly lower IL-4 and IL-6 concentrations in alexithymic than in non-alexithymic patients. According to multiple linear regression analysis, alexithymia predicted low IL-4 and IL-6 levels in the sample overall, independently of stress, anxiety, depression and other possible confounders. No between-group differences were found in serum levels of IFN-γ, IL-1ß, and TNF-α. CONCLUSION: These findings argue against an isolated shift towards pro-inflammatory or anti-inflammatory mediators and suggest that circulating cytokine profiles differ in alexithymic and non-alexithymic subjects.
Assuntos
Sintomas Afetivos/imunologia , Citocinas/sangue , Endoscopia do Sistema Digestório , Adulto , Sintomas Afetivos/sangue , Sintomas Afetivos/psicologia , Estudos Transversais , Endoscopia do Sistema Digestório/efeitos adversos , Endoscopia do Sistema Digestório/psicologia , Feminino , Humanos , Interferon gama/sangue , Interleucina-10/sangue , Interleucina-1beta/sangue , Interleucina-4/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Análise de Regressão , Estresse Psicológico/imunologia , Fator de Necrose Tumoral alfa/sangueRESUMO
Chronic obstructive pulmonary disease (COPD) is an alteration in which ventilatory function, exercise capacity and health status of patients progressively decline and it is characterized by an increase of inflammatory cytokines such as TNF-α, LTB4, IL-8, etc. In this study we considered twenty patients (15 males and 5 females; mean age: 72.8 ± 6.3) with stable COPD. All patients were performed evaluation of psychological stress at enrollment and were treated with leukotriene receptor antagonists (montelukast tablets) 10mg/day for 12 months. After 12 months we observed a significant decrease of serum levels of LTB4, IL-8 and also a decrease of the number of outpatient clinic visits, of the number of hospitalizations and of the duration of hospitalization.
Assuntos
Acetatos/uso terapêutico , Antiasmáticos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/psicologia , Quinolinas/uso terapêutico , Estresse Psicológico/etiologia , Idoso , Ciclopropanos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Interleucina-8/sangue , Leucotrieno B4/sangue , Masculino , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Sulfetos , Fator de Necrose Tumoral alfa/sangueRESUMO
UNLABELLED: The known role of heat-shock proteins (HSPs) in the pathogenesis of atherosclerosis prompted us to investigate whether HSP90 is a target autoantigen of immune responses in patients with carotid atherosclerosis. METHODS AND RESULTS: The presence of HSP90 on 26 cryostat and 6 paraffin embedded sections of carotid atherosclerotic plaques was determined by immunohistochemistry and immunofluorescence. Plaque-infiltrating T lymphocytes from 9 patients and circulating PBMC from 26 patients and 21 healthy subjects were tested by cell proliferation assay and by flow cytometry and ELISA for cytokine production in response to HSP90. ELISA was used to detect soluble HSP90 and anti-HSP90 antibodies in serum samples. Strong HSP90 immunoreactivity was detected in the muscle and endothelial cell layer and in the inflammatory infiltrate of carotid plaques. Plaque-derived and circulating T lymphocytes from patients proliferated in response to HSP90 whereas cells from healthy subjects did not. HSP90-specific T lymphocytes expressed IFN-gamma and IL-4 suggesting concomitant Th1 and Th2 activation. ELISA detected soluble HSP90 in 42% and anti-HSP90 antibodies in 46% of patients' sera. CONCLUSIONS: These new findings, showing that HSP90 is overexpressed in plaque and serum from patients with atherosclerosis and induces an immune response in these patients, implicate HSP90 as a possible target autoantigen in the pathogenesis of carotid atherosclerosis.
Assuntos
Autoanticorpos/sangue , Autoantígenos/imunologia , Doenças das Artérias Carótidas/imunologia , Proteínas de Choque Térmico HSP90/imunologia , Linfócitos T/imunologia , Idoso , Idoso de 80 Anos ou mais , Autoantígenos/sangue , Doenças das Artérias Carótidas/sangue , Estudos de Casos e Controles , Proliferação de Células , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Imunofluorescência , Proteínas de Choque Térmico HSP90/sangue , Humanos , Imunidade Celular , Imunidade Humoral , Imuno-Histoquímica , Imunofenotipagem , Interferon gama/metabolismo , Interleucina-4/metabolismo , Ativação Linfocitária , Masculino , Pessoa de Meia-IdadeRESUMO
Studies aimed at elucidating the pathogenetic mechanisms underlying the initiation and progression of human atherosclerosis have emphasized the central role of inflammatory and immune cells. Atherosclerotic plaques are infiltrated by activated macrophages, T and B lymphocytes, plasma cells, and mast cells, releasing inflammatory molecules, which amplify the severity of the disease. Endothelial cells subjected to various stress conditions express increased amounts of heat shock proteins (HSPs), some of the most successfully conserved proteins throughout evolution. Many experimental observations reviewed in this article draw attention to several HSPs targeted by a specific cellular and humoral immune response in patients with atherosclerotic disease. The review also reports preliminary data obtained by our group on the possible role of HSP90 as a candidate autoantigen in carotid atherosclerosis. Our study deals with the presence of specific antibodies and T cells directed against HSP90 in patients with carotid atherosclerotic plaques. In 60% of these subjects' sera but in none of the sera from healthy controls immunoblotting (IB) detected the presence of specific antibodies. Moreover, 20% of peripheral blood mononuclear cells (PBMC) samples from patients but none from healthy subjects proliferated in response to human purified HSP90. In vitro experiments showed an upregulation of HSP90 expression in endothelial cells exposed to oxidative stress by treatment with H(2)O(2) and greater release of soluble HSP90 in culture supernatants from H(2)O(2)-treated cells than from untreated cells.
Assuntos
Arteriosclerose/imunologia , Arteriosclerose/metabolismo , Autoimunidade/imunologia , Doenças das Artérias Carótidas/imunologia , Doenças das Artérias Carótidas/metabolismo , Proteínas de Choque Térmico/metabolismo , Animais , Autoantígenos/imunologia , Proteínas de Choque Térmico/classificação , HumanosRESUMO
PURPOSE: Rhinoscleroma is a rare, chronic, granulomatous disorder of the upper airways. This disease presents some etiopathogenetic aspects that are not yet clear. Infection by Klebsiella rhinoscleromatis is fundamental for the onset of the disease, but it is impossible to reproduce rhinoscleroma experimentally only via infection with the bacteria both in man and in animals. Furthermore, this disease mainly affects blood-related people and occurs in certain geographic areas. In this context, we present a study that brings to light some of the quantitative abnormalities of the lymphocyte subsets. MATERIALS AND METHODS: The study group consisted of 5 patients with rhinoscleroma. The following parameters were studied for each patient: clinical manifestations, histologic examinations, number of leukocytes, lymphocytes, and lymphocyte subsets. RESULTS: In all patients, we noted the following: There was a relative reduction of the CD4+ cells, an absolute increase of the CD8+ cells, and an inversion of the CD4+/CD8+ ratio. There was an absolute increase of the CD56+ cells and cytotoxic cells that coexpress CD8+CD56+ antigens. There was a relative reduction of the CD3+ cells, and the CD19+ cells tended to show an ambiguous behavioral pattern. CONCLUSION: We believe that K. rhinoscleromatis does not play a major role in the etiopathogenesis of rhinoscleroma. However, we do believe that the anomalous behavior of the immune system can favor rhinoscleroma.
Assuntos
Infecções por Klebsiella/imunologia , Klebsiella pneumoniae , Subpopulações de Linfócitos/imunologia , Rinoscleroma/imunologia , Adulto , Antígenos CD/análise , Relação CD4-CD8 , Feminino , Humanos , Contagem de Linfócitos , Subpopulações de Linfócitos/microbiologia , Masculino , Pessoa de Meia-Idade , Rinoscleroma/microbiologiaRESUMO
The interleukins (IL)-6 and -10 and heat shock proteins (HSP) have an important role in the host-tumor interaction and in tumor bulk. HSP-90 may have a regulatory role in cytokine biosynthesis and prognostic value in some tumors. To define the role of IL-6, IL-10 and HSP-90 in prostate cancer progression the immunohistochemical expressions of these proteins were analyzed in 168 prostatic carcinomas. IL-6, IL-10 and HSP-90 immunoreactivity was higher in prostatic carcinoma (CaP) and intra-epithelial prostatic neoplasia (PIN) than in normal prostatic tissue (NAP) adjacent to neoplasia. In the epithelium, IL-6, IL-10 and HSP-90 expressions increased from NAP to PIN to CaP. In the stroma, IL-6 and IL-10 expressions decreased significantly from NAP to PIN to CaP (p < 0.01 by Chi-square test), while HSP-90 expression increased. In the epithelium of PIN and CaP, IL-6 immunoreactivity was significantly lower than IL-10 and HSP-90. In neoplastic acini HSP-90 levels were significantly higher than those of IL-6 and IL-10 (p < 0.01 by Chi-square test). In the stroma of NAP and PIN, but not of CaP, HSP-90 immunoreactivity was significantly lower than that of IL-6 and IL-10 (p < 0.01). Our results indicate that the IL-6 and IL-10 cytokine balance differs in pathological and normal prostate, thus suggesting that certain cytokines are specific to the neoplastic prostate. Changes in the expressions of IL-6, IL-10 and HSP-90 in human prostate carcinoma samples could be used as a prognostic marker of disease progression.
Assuntos
Proteínas de Choque Térmico HSP90/metabolismo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Neoplasias da Próstata/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Próstata/metabolismo , Próstata/patologia , Prostatectomia , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patologia , Hiperplasia Prostática/cirurgia , Neoplasia Prostática Intraepitelial/metabolismo , Neoplasia Prostática Intraepitelial/patologia , Neoplasia Prostática Intraepitelial/cirurgia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Análise Serial de TecidosRESUMO
While the clinical and immunologic efficacy of sublingual immunotherapy (SLIT) in allergic diseases has been extensively demonstrated, some patients display a poor clinical response. Psychological stress has been shown to play a role in atopy and also to affect response to immunomodulating therapies such as vaccination with microbial antigens. This study addresses the possibility of response to SLIT being affected by psychological stress. Forty children with mild asthma caused by allergy to Dermatophagoides pteronyssinus and farinae were subjected to SLIT and then divided after 6 months into two groups based on the results of the stress integrated measure (SIM) test: group 1 (24 stressed patients, mean SIM value of 60.1) and group 2 (16 non-stressed patients, mean SIM value of 7.6). There was also a higher prevalence of psychosocial stressing factors (divorced/absent parents, low income households, non-working parents) among stressed patients. The symptom score, peak expiratory flow (PEF), forced expiratory volume in 1 s (FEV(1)) and serum eosinophie cationic protein (ECP) concentration were evaluated at both times. The serum concentration of neuroendocrine parameters [prolactin, cortisol, adrenocorticotropic hormone (ACTH)] was also measured after 6 months of therapy. While all the clinical parameters and ECP concentration improved after SLIT, symptom score, PEF and ECP showed a significantly greater improvement in non-stressed patients. The concentration of neuroendocrine parameters was significantly increased in stressed patients. Our findings show that psychological stress can affect response to SLIT also in allergic subjects and are consistent with data recently reported showing a correlation between stress and poor response to antimicrobial vaccines. Our data also suggest that stress evaluation may become a useful prognostic factor in immunotherapy.
Assuntos
Antígenos de Dermatophagoides/imunologia , Asma/imunologia , Asma/psicologia , Imunoterapia/psicologia , Estresse Fisiológico/imunologia , Administração Sublingual , Adolescente , Hormônio Adrenocorticotrópico/sangue , Adulto , Antígenos de Dermatophagoides/administração & dosagem , Antígenos de Dermatophagoides/efeitos adversos , Asma/sangue , Asma/terapia , Criança , Proteína Catiônica de Eosinófilo/sangue , Proteína Catiônica de Eosinófilo/imunologia , Feminino , Humanos , Imunoterapia/métodos , Masculino , Pico do Fluxo Expiratório/fisiologia , Prolactina/sangue , Estresse Fisiológico/sangue , Células Th1/imunologia , Células Th2/imunologiaRESUMO
OBJECTIVE: Leptin, an adipocyte-secreted hormone, has emerged as a potential candidate for the link between obesity and the proinflammatory state. Specifically, leptin modulates T-helper (Th) cells toward a Th1 phenotype, with the secretion of proinflammatory cytokines. The aim of this study was to evaluate the Th1/Th2 balance in obese children and its relation with hormonal and metabolic features. STUDY DESIGN: In 50 obese children and 20 control children, we measured the CD4-positive Th cells that secrete interferon (IFN)-gamma or interleukin (IL)-2 (taken as an index of Th1 cells), and IL-4 (taken as an index of Th2 cells) as well as serum glucose, insulin, insulin resistance (IR) index (as homeostasis model assessment model (HOMA)), lipid profile, aminotransferases, leptin and ghrelin. Obese children also underwent dual energy X-ray absorptiometry scan measurements, and liver ultrasound scanning. RESULTS: Geometric mean percentages of IL-2- and IL-4-CD4 secreting cells in obese children were not significantly different from those found in control children. However, the geometric mean percentage of CD4-positive T cells secreting IFN-gamma was significantly higher in the obese than in the control (P < 0.0001, t-test) group. Within the entire group of study children, the percentage of IFN-gamma-positive cells was positively associated with leptin (P = 0.002), insulin (P < 0.00 005), and HOMA-IR values (P < 0.00 005). However, when these associations were restricted to the group of obese subjects, insulin and HOMA-IR values, but not leptin, retained statistical significance. Yet, in the obese group, the percentage of IFN-gamma-positive cells was associated with nonalcoholic steatohepatitis (NASH) (P = 0.001), but not with body mass index-standard deviation score and total body fat mass. CONCLUSIONS: In obese children, a shift to Th1-cytokine profile dominated by the production of IFN-gamma is related to insulin resistance as well as to NASH independently of anthropometric features and other metabolic characteristics. The prevalent Th1 pattern of secreted cytokines may be regarded as a mechanism contributing to inflammation in obesity.
Assuntos
Interferon gama/imunologia , Obesidade/imunologia , Células Th1/imunologia , Biomarcadores , Criança , Feminino , Humanos , Inflamação/imunologia , Interferon gama/metabolismo , Interleucina-2/metabolismo , Interleucina-4/metabolismo , Leptina/imunologia , Leptina/metabolismo , Masculino , Células Th1/metabolismo , Células Th2/imunologia , Células Th2/metabolismoAssuntos
Proteínas de Choque Térmico/fisiologia , Vitiligo/metabolismo , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Feminino , Humanos , Sistema Imunitário/patologia , Inflamação , Interleucina-2/sangue , Leucócitos/citologia , Contagem de Linfócitos , Linfócitos/citologia , Masculino , Vitiligo/genéticaRESUMO
OBJECTIVE: To develop a multiple-endpoint monitoring system in order to assess and minimize long term risks in hospital nurses exposed to antiblastic drugs. DESIGN: Molecular epidemiology study. SETTING: S. Orsola-Malpighi Hospital in Bologna, Italy: nurses exposed to antiblastic drugs. PARTICIPANTS: 50 exposed subjects (8 males and 42 females) and 50 unexposed individuals (8 males and 42 females) matched for age and smoking habits. MAIN OUTCOME MEASURES: Urinary markers of exposure, Heat Shock Proteins (HSPs) 27, 70, 90, 110, immunologic biomarkers in peripheral blood lymphocytes: apoptosis, cell-cycle analysis G1-S-G, typization of Natural Killer cells (NK) and receptors micronuclei; frequency in peripheral blood lymphocytes and in exfoliated buccal mucosa cells; activation ofspecific oncogenes (bax, bcl2). RESULTS: 19/50 subjects showed urinary antiblastic drug levels (3 subjects MTX, 11 subjects CP, 5 subjects MTX and CP). No statistically significant differences were observed in all the considered biomarkers between the exposed and control groups. CONCLUSION: This biomonitoring study doesn't evidence any early significant effect associated to the exposure to antiblastic drugs.
Assuntos
Antineoplásicos/urina , Monitoramento Ambiental , Enfermeiras e Enfermeiros , Exposição Ocupacional/análise , Adulto , Feminino , Humanos , MasculinoRESUMO
OBJECT: To evaluate the role of local inflammation in the pathogenesis and postoperative recurrence of chronic subdural hematoma (CSDH), the authors conducted an investigation in a selected group of patients who could clearly recall a traumatic event and who did not have other risk factors for CSDH. Inflammation was analyzed by measuring the concentration of the proinflammatory and inflammatory cytokines interleukin (IL)-6 and IL-8. The authors also investigated the possible relationship between high levels of local inflammation that were measured and recurrence of the CSDH. METHODS: A prospective study was performed between 1999 and 2001. Thirty-five patients who could clearly recall a traumatic event that had occurred at least 3 weeks previously and who did not have risk factors for CSDH were enrolled. All patients were surgically treated by burr hole irrigation plus external drainage. The concentration of inflammatory cytokines was very high in the lesion, whereas it was normal in serum. In five cases in which recurrence occurred, concentrations of both IL-6 and IL-8 were significantly increased (p < 0.01) in comparison with cases without a recurrence. In a layering hematoma, the IL-6 and IL-8 concentrations were significantly higher (p < 0.05). Layering CSDHs were also significantly correlated with recurrence. Trabecular hematoma had the lowest cytokine levels and the longest median interval between trauma and clinical onset. The interval from trauma did not significantly influence recurrence, although it did differ significantly between the trabecular and layering CSDH groups. Concentrations of IL-6 and IL-8 in the CSDHs did not differ significantly in relation to either the age of the hematoma (measured as the interval from trauma) or the age of the patient. CONCLUSIONS: Brain trauma causes the onset of an inflammatory process within the dural border cell layer; high levels of inflammatory cytokines were significantly correlated with recurrence and layering CSDH. A prolonged postoperative antiinflammatory medicine given as prophylaxis may help prevent the recurrence of a CSDH.
Assuntos
Hematoma Subdural Crônico/epidemiologia , Hematoma Subdural Crônico/imunologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Hemorragia Encefálica Traumática/epidemiologia , Hemorragia Encefálica Traumática/imunologia , Proteína C-Reativa/metabolismo , Feminino , Humanos , Interleucina-6/sangue , Interleucina-8/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Fatores de RiscoRESUMO
The clinical efficacy of sublingual immunotherapy (SLIT) has been demonstrated, but its mechanism of action is still controversial. The most recent experimental observations suggest that a critical role in the modulation of immune response is sustained by Th2 cytokines, such as interleukin-4 (IL-4), IL-5 and IL-13, by co-stimulatory molecules, such as CD40 on B cells, and by hormones and neuropeptides. To better understand whether SLIT affects immune responses we used a double-blind placebo-controlled design. Eighty-six children with mild asthma due to allergy to Dermatophagoides pteronyssinus (33 of whom also had rhinoconjunctivitis) were randomly assigned SLIT (n = 47) or placebo (n = 39). We assessed symptom scores using diary cards of each patient and determined the expression of CD40 on B cells and the serum concentration of ECP, IL-13, prolactin (PRL) and ACTH at enrolment and after 6 months of therapy. We observed a significant reduction in asthma and rhinitis scores in the immunotherapy group compared with the placebo group, no variation in CD40 and ACTH, but a significant decrease in ECP, IL-13 and PRL after 6 months of therapy (p <0.01). Our results confirm the efficacy and safety of SLIT, and lead us to believe that it could modulate the synthesis of Th2 cytokines, as revealed from the decrease of IL-13. In addition, the reduction of PRL might be a signal of reduced activation of T lymphocytes.
Assuntos
Hormônio Adrenocorticotrópico/biossíntese , Asma/imunologia , Asma/terapia , Dermatophagoides pteronyssinus/imunologia , Imunoterapia , Interleucina-13/biossíntese , Prolactina/biossíntese , Rinite Alérgica Perene/terapia , Administração Sublingual , Alérgenos/administração & dosagem , Alérgenos/imunologia , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Masculino , Rinite Alérgica Perene/imunologia , Testes CutâneosRESUMO
BACKGROUND: Several studies found a high incidence rate of neuro-psychiatric complications during long-term therapy with interferon alpha (IFNalpha), e.g. slowness, severe fatigue, hypersomnia, lethargy, depressed mood, mnemonic troubles, irritability, short temper, emotional lability, social withdrawal, and lack of concentration. The aim of this study was to examine the incidence of depressed mood and major depression in patients who were treated with IFNalpha. METHODS: 30 patients, affected by chronic active C-hepatitis, have been evaluated at baseline and 3 months after IFNalpha treatment. The evaluation consisted of psychometric assessments employing the DSM-IV criteria and the Montgomery Asberg Depression Rating Scale (MADRS). RESULTS: At end-point, 40.7% of the patients suffered from a full blown major depression, according to the DSM-IV criteria for major depression. IFNalpha treatment induced a significant increase in the MADRS score from baseline to 3 months later. The MADRS items which were significantly increased at end-point were: expressed and unexpressed sadness; irritability; insomnia; loss of appetite; and asthenia. DISCUSSION: The results show that prolonged IFNalpha treatment may induce depressive symptoms and major depression in a considerable number of subjects.
Assuntos
Antivirais/efeitos adversos , Antivirais/uso terapêutico , Transtorno Depressivo/induzido quimicamente , Hepatite C/tratamento farmacológico , Interferon-alfa/efeitos adversos , Interferon-alfa/uso terapêutico , Afeto/efeitos dos fármacos , Idoso , Transtorno Depressivo/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: To observe the plasmatic concentration of IL-6, IL-10 and IL-2 in the patient of chronic allergic rhinitis before and after acupuncture therapy. METHODS: Cytokine levels were determined before and after treatment in 30 healthy volunteers (Group A) and 90 patients of chronic allergic rhinitis (Group B) with an increased plasma IL-10 level. Group B was then divided into 3 subgroups: 30 patients treated with real acupuncture (Group B1); 30 patients treated with sham acupuncture (Group B2); 30 non-treated patients (Group B3). RESULTS: The allergic subjects of group B1, compared with controls, showed a significant reduction of IL-10 after a specific treatment with acupuncture (P < 0.05). On the other hand, in those patients treated with sham acupuncture (B2) as well as in non-treated patients (B3), the IL-10 values remained high and unchanged. There was a statistically significant change in IL-2 values at 24 hours (P < 0.05) after real acupuncture (Groups A, B1), however the values remained within normal ranges. The IL-6 do not change after therapy. CONCLUSION: The acupuncture treatment can reduce plasmatic level of IL-10 in chronic allergic rhinitis.