RESUMO
Major depressive disorder (MDD) has a prevalence of 5% in adolescents. Several studies have described the association between the inflammatory response and MDD, but little is known about the relationship between MDD and growth factors, such as IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF. It must be appointed that there are scarce reports on growth factors in adolescents with MDD and even fewer with a clinical follow-up. In this work, we evaluated the levels of growth factors (IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF) in MDD adolescents and the clinical follow-up during eight weeks of treatment with fluoxetine. Methods. All patients were diagnosed according to the DSM-IV-TR, and the severity of the symptoms was evaluated using the Hamilton Depression Rating Scale (HDRS). Growth factors IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF were quantified by cytometric bead array using serum samples from 22 adolescents with MDD and 18 healthy volunteers. Results. All patients showed clinical improvement since the fourth week of pharmacological treatment according to the HDRS. Considerably higher levels of IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF were detected in MDD adolescents as compared to healthy volunteers. A significant but temporal decrease was detected in basic FGF, G-CSF, and GM-CSF at week four of fluoxetine administration. Conclusions. To the best of our knowledge, this is the first report to show alterations in the levels of growth factors, such as IL-7, IL-9, IL-17A, VEGF, basic FGF, G-CSF, and GM-CSF in MDD adolescents during eight weeks of clinical follow-up. These disturbances might be involved in the physiopathology of MDD since such growth factors have been proven to participate in the neural development and correct functioning of the CNS; therefore, subtle alterations in it may contribute to MDD.
Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Fluoxetina/uso terapêutico , Adolescente , Adulto , Transtorno Depressivo Maior/sangue , Feminino , Fator 2 de Crescimento de Fibroblastos/sangue , Fator Estimulador de Colônias de Granulócitos/sangue , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Humanos , Interleucina-17/sangue , Interleucina-7/sangue , Interleucina-9/sangue , Estudos Longitudinais , Masculino , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto JovemRESUMO
BACKGROUND: Falls are common among elderly adults, and are predictors of hospitalization, institutionalization and mortality. OBJECTIVE: The objective of the present study was to examine the relationship between blood-based markers of inflammation and fall events in a sample of elderly Hispanic adults. METHOD: Data were collected from 190 participants enrolled in the Panama Aging Research Initiative study who completed baseline clinical and cognitive assessments. A non-fasting blood sample was obtained. Self-reported falls were classified as no falls, single falls or recurrent (two or more) falls reported in the 12 months prior to baseline evaluations. Serum levels of C Reactive Protein (CRP), T-lymphocyte secreting protein (I-309), interleukin 10 (IL-10), interleukin 6 (IL-6) and interleukin 7 (IL-7) were measured. Global cognition was assessed with the Mini Mental State Examination and depressive symptoms were assessed with the Geriatric Depression Scale (GDS-30). Multinomial logistic regression was used to assess the link between inflammation and fall events. RESULTS: Depressive symptoms, limitations in Instrumental Activities of Daily Living (IADL), IL-7 and I-309 were significantly related to fall events. Elevated levels of IL-7 increased the likelihood of single and recurrent falls, while increased levels of I-309 were associated only with recurrent falls. Greater IADL limitations and depressive symptoms were associated with an increased likelihood of recurrent falls. CONCLUSION: There is a lack of research investigating the relationship between inflammatory biomarkers and fall events. These results provide evidence of risk factors for falls in Hispanic older adults, and could serve to guide public health professionals to establish clinical guidelines to reduce fall risks.
Assuntos
Acidentes por Quedas , Envelhecimento/sangue , Envelhecimento/psicologia , Depressão/sangue , Mediadores da Inflamação/sangue , Acidentes por Quedas/prevenção & controle , Acidentes por Quedas/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Quimiocina CCL1/sangue , Depressão/complicações , Feminino , Hispânico ou Latino , Humanos , Incidência , Interleucina-10/sangue , Interleucina-6/sangue , Interleucina-7/sangue , Masculino , Panamá/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: The severity of cardiac disease in chronic Chagas disease patients is associated with different features of T-cell exhaustion. Here, we assessed whether the ability of T cells to secrete IFN-γ in response to T. cruzi was linked to disruption in immune homeostasis and inflammation in patients with chronic Chagas disease. METHODOLOGY/PRINCIPAL FINDINGS: PBMCs from chronic Chagas disease patients and uninfected controls were examined for frequencies of T. cruzi-responsive IFN-γ-producing cells by ELISPOT and cellular expression and function of IL-7R using flow cytometry. Serum levels of IL-7, IL-21, IL-27, soluble IL-7R, and inflammatory cytokines were also evaluated by ELISA or CBA techniques. Patients possessing T. cruzi-specific IFN-γ-producing cells (i.e. IFN-γ producers) had higher levels of memory T cells capable of modulating the alpha chain of IL-7R and an efficient response to IL-7 compared to that in patients lacking (i.e. IFN-γ nonproducers) parasite-specific T-cell responses. IFN-γ producers also showed low levels of soluble IL-7R, high basal expression of Bcl-2 in T cells and low basal frequencies of activated CD25+ T cells. Modulation of IL-7R was inversely associated with serum IL-6 levels and positively associated with serum IL-8 levels. Circulating IL-21 and IL-27 levels were not associated with the frequency of IFN-γ producing cells but were reduced in less severe clinical forms of the disease. In vitro stimulation of PBMCs with IL-7 or IL-27 enhanced IFN-γ production in IFN-γ producers but not in IFN-γ nonproducers. CONCLUSIONS/SIGNIFICANCE: Alterations of the IL-7/IL-7R axis and in the levels of inflammatory cytokines were linked to impaired T. cruzi-specific IFN-γ production. These alterations might be responsible of the process of immune exhaustion observed in chronic Chagas disease.
Assuntos
Doença de Chagas/sangue , Interferon gama/sangue , Interleucina-7/sangue , Receptores de Interleucina-7/metabolismo , Trypanosoma cruzi/fisiologia , Adulto , Idoso , Doença de Chagas/genética , Doença de Chagas/parasitologia , Doença Crônica , ELISPOT , Feminino , Humanos , Interferon gama/genética , Interleucina-7/genética , Interleucinas/sangue , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Receptores de Interleucina-7/genética , Linfócitos T/metabolismo , Trypanosoma cruzi/genética , Adulto JovemRESUMO
Introducción. El caseinato de sodio, una sal de la caseína utilizada como agente proinflamatorio en ratones, es capaz de inducir granulopoyesis en vivo e incrementar la producción de citocinas esenciales en dicho evento.Objetivo. Evaluar si el caseinato de sodio es capaz de inducir un efecto biológico en células de origen linfoide y la producción de citocinas involucradas con este linaje.Materiales y métodos: Se utilizaron ratones hembra BALB/c de 8 a 12 semanas de edad. Los animales se inyectaron cuatro veces, con intervalos de 48 horas, por vía intraperitoneal con 1 ml de caseinato de sodio (10 % de SFB p/v). La población de linfocitos B y la incorporación de bromodesoxiuridina (BrdU) se analizaron mediante citometría de flujo. La detección de la interleucina 7 se evaluó mediante la técnica de ELISA.Resultados. Tras la inyección por vía intraperitoneal, el número de linfocitos B 220+ provenientes del bazo de ratones tratados con caseinato de sodio aumentó comparados con los que solo recibieron el vehículo como tratamiento (89,01±1,03 Vs. 75,66±2,08), así como la incorporación de BrdU en células B220+ (38,59±4,48 Vs. 11,82±1,04). Se evidenció, asimismo, el incremento en la concentración de la interleucina 7 (IL-7) en el suero de los ratones tratados con caseinato de sodio, comparados con los que solo recibieron el vehículo (62,1±17,5 Vs. 26,9±4,4 pg/ml).Conclusión. El caseinato de sodio fue capaz de aumentar el número de linfocitos B en bazo de ratones, así como inducir la producción de IL-7, citocina clave para la linfopoyesis B.
Assuntos
Linfócitos B/efeitos dos fármacos , Caseínas/farmacologia , Linfopoese/efeitos dos fármacos , Animais , Medula Óssea/efeitos dos fármacos , Caseínas/administração & dosagem , Caseínas/toxicidade , Divisão Celular , Feminino , Injeções Intraperitoneais , Interleucina-7/biossíntese , Interleucina-7/sangue , Interleucina-7/genética , Contagem de Linfócitos , Linfocinas/biossíntese , Linfocinas/genética , Camundongos , Camundongos Endogâmicos BALB C , Baço/citologia , Baço/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacosRESUMO
BACKGROUND: Leptospirosis is a health problem worldwide. Its most severe form is a classic model of sepsis, provoking acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI), with associated mortality that remains unacceptably high. We previously demonstrated that early initiation of sustained low-efficiency dialysis (SLED) followed by daily SLED significantly decreases mortality. However, the mode of clearance can also affect dialysis patient outcomes. Therefore, the objective of this study was to compare the effects of SLED with traditional (diffusive) clearance, via hemodialysis, and SLED with convective clearance, via hemodiafiltration (SLEDf), in patients with severe leptospirosis. METHODS: In this prospective study, conducted in the intensive care unit (ICU) from 2009 through 2012, we compared two groups-SLED (n = 19) and SLEDf (n = 20)-evaluating demographic, clinical, and biochemical parameters, as well as serum levels of interleukins, up to the third day after admission. All patients received dialysis early and daily thereafter. RESULTS: During the study period, 138 patients were admitted to our ICU with a diagnosis of leptospirosis; 39 (36 males/3 females) met the criteria for ARDS and AKI. All patients were on mechanical ventilation and were comparable in terms of respiratory parameters. Mortality did not differ between the SLEDf and SLED groups. However, post-admission decreases in the serum levels of interleukin (IL)-17, IL-7, and monocyte chemoattractant protein-1 were significantly greater in the SLEDf group. Direct bilirubin and the arterial oxygen tension/fraction of inspired oxygen ratio were significantly higher in the SLED group. We identified the following risk factors (sensitivities/specificities) for mortality in severe leptospirosis: age ≥ 55 years (67%/91%); serum urea ≥ 204 mg/dl (100%/70%); creatinine ≥ 5.2 mg/dl (100%/58%); Acute Physiology and Chronic Health Evaluation II score ≥ 39.5 (67%/88%); Sequential Organ Failure Assessment score ≥ 20.5 (67%/85%); and inspiratory pressure ≥ 31 mmHg (84%/85%). CONCLUSIONS: The mode of dialysis clearance might not affect outcomes in severe leptospirosis.
Assuntos
Hemodiafiltração , Mediadores da Inflamação/sangue , Leptospirose/terapia , Injúria Renal Aguda/sangue , Injúria Renal Aguda/complicações , Injúria Renal Aguda/terapia , Adulto , Idoso , Quimiocina CCL2/sangue , Feminino , Humanos , Unidades de Terapia Intensiva , Interleucina-17/sangue , Interleucina-7/sangue , Leptospirose/sangue , Leptospirose/patologia , Masculino , Pessoa de Meia-Idade , Síndrome do Desconforto Respiratório/sangue , Síndrome do Desconforto Respiratório/complicações , Síndrome do Desconforto Respiratório/terapia , Sepse/sangue , Sepse/complicações , Sepse/terapia , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The conjoint effect of HIV infection and pregnancy on the immune system of women submitted to the prophylactic antiretroviral therapy presently recommended is still poorly understood. METHODS: We evaluated 44 HIV-infected women (HIV) and 45 HIV-negative women (CT) at parturition and we compared them to 20 healthy nonpregnant women (NP). Immunophenotyping of lymphocytes was done by four-color flow cytometry. RESULTS: All HIV-infected women received HAART during pregnancy and 56.8% had viral load <50 copies/mL at delivery. CD4+T cells/mm(3) were lower in HIV (447) than CT (593) and NP (738) (P < 0.05). CD8+T cells/mm(3) were higher in HIV (799) than CT (384) and NP (395) (P < 0.05). NK cells/mm(3) were lower in HIV (146) than in CT (253) and NP (198) (P < 0.05). CD38 expression on CD4+T and on CD8+T cells was higher in HIV (CD4:12.1; CD8:14.9) than in CT(CD4:9.2; CD8:10.2) and NP(CD4:8.6; CD8:6.0) (P < 0.05). However, CD56 expression on CD8+T cells (a marker of cytolytic effector function) was lower in HIV(7%) than in CT(12%) and NP(9%) (P < 0.05). CONCLUSIONS: Even with low levels of viremia, HIV-infected women at delivery showed a different immunologic profile from both healthy non-HIV-infected women in the puerperium and nonpregnant women, with lower CD4+T and higher CD8+T cells, high levels of CD38 expression, but low CD56 expression on CD8+T cells and low NK cell numbers.
Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , HIV-1/imunologia , Complicações Infecciosas na Gravidez , ADP-Ribosil Ciclase 1/imunologia , Adolescente , Adulto , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Feminino , Infecções por HIV/sangue , Soropositividade para HIV , Humanos , Imunofenotipagem , Interleucina-7/sangue , Interleucina-7/imunologia , Células Matadoras Naturais/imunologia , Ativação Linfocitária , Contagem de Linfócitos , Gravidez , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/virologia , Subpopulações de Linfócitos T/imunologia , Carga Viral , ViremiaRESUMO
BACKGROUND: HIV-1 infection results in severe immunodeficiency when T-cell loss cannot be compensated. IL-7 is one of the main cytokines involved in the maintenance of T-cell homeostasis. However, IL-7 can also enhance HIV-1 replication in vivo and lead to an accelerated progression of AIDS. OBJECTIVE: The aim of our study was to evaluate if the increase of IL-7 levels in response to CD4+ T cell depletion could favor the emergence of HIV-1 strains with more aggressive phenotypes in pediatric infection. STUDY DESIGN: Plasma IL-7 levels were measured in 42 HIV-1 vertically infected infants at different times of infection, and HIV-1 isolates were obtained from primary cell cultures to determine replication rate and syncytium-inducing (SI) capability on MT-2 cell line. RESULTS: IL-7 levels were significantly higher in infants harboring HIV-1 SI strains compared to those with non-syncytium-inducing (NSI) viruses (p<0.0001). Likewise, IL-7 levels were higher in infants with rapid replicating viral strains versus those with slow replicating viruses (p=0.0006). Despite the strong negative correlation between IL-7 levels and CD4+ T lymphocyte counts (r=-0.55, p=0.0001), covariance analysis demonstrated that the high levels of IL-7 were associated with more virulent phenotype features (SI and rapid replicating strains) independently of CD4+ T cell depletion. In 19 of the 42 infants, longitudinal follow-up studies showed that SI to NSI phenotype switch can occur after HAART administration, with a reduction in IL-7 levels and an increase in CD4+ T cell counts. CONCLUSIONS: IL-7 response to T-cell depletion may enhance T-cell production, but at the same time may foster HIV-1 disease progression favoring the emergence of more virulent HIV-1 strains characterized by SI capability and rapid replication rate.
Assuntos
Infecções por HIV/virologia , HIV-1/patogenicidade , Interleucina-7/sangue , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Criança , Pré-Escolar , Infecções por HIV/imunologia , HIV-1/classificação , HIV-1/genética , Humanos , Lactente , Leucopenia , VirulênciaRESUMO
OBJECTIVES: Growth hormone (GH) plays a role in thymic function, and recombinant GH may stimulate thymopoiesis in HIV-infected individuals. We performed immunologic analyses in 26 antiretroviral-treated children matched for age, pubertal status, clinical parameters, and antiretroviral exposure who did or did not show an impaired response to GH-release stimulation tests with arginine + GH-releasing hormone. RESULTS: The following abnormalities were found in GH-deficient compared with GH-nondeficient children after >4 years of therapy: CD4 count ( P = .02) and percentage ( P = .03), CD4 as percentage of normal cells for age ( P = .003), serum interleukin-7 concentration ( P = .02), and thymic volume ( P = .01). Naive CD4 (4+62+RA+ and 4+CCR7+RA+) and CD8 (8+CCR7+RA+) lymphocytes were lower in GH-deficient children ( P = .003; P = .007; and P = .02, respectively). Postthymic pathways were also impaired in GH-deficient children. Thus, central memory (4+CCR7+RA-) CD4+ cells were reduced ( P = .006), whereas effector memory (4+CCR7-RA-) CD4+ cells ( P = .002) and late effector CD8+ lymphocytes (8+CCR7-RA+ and 8+27-28-) ( P = .009 and P = .002, respectively) were increased in these children. CONCLUSIONS: Growth hormone plays a role in thymic and postthymic pathways, and defective GH production may be associated with incomplete immunoreconstitution. Immunomodulant agents (including GH) could be useful in patients with defective GH production.