IL-6 levels are associated with clinical status in patients with Myasthenia Gravis / Os níveis de IL-6 estão associados com o status clínico de pacientes com Miastenia Gravis

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease marked by fluctuating course of muscle weakness. OBJECTIVES: The current study was designed to evaluate plasma levels of cytokines (IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, and IL17A) in patients with MG and controls and to investigate whether cytokines levels are associated with clinical parameters. This study was conducted at the Neuromuscular Diseases Outpatient Clinic, Hospital das Clínicas, Universidade Federal de Minas Gerais (UFMG), Brazil. METHODS: Peripheral blood was drawn, and plasma levels of cytokines were measured by cytometric bead array (CBA) in 80 treated patients with MG and 50 controls. The MG Composite (MGC) was used to evaluate muscle weakness and severity of typical motor symptoms of MG. RESULTS: Patients with MG undergoing treatment exhibit lower levels of all evaluated cytokines compared to controls. There was a negative correlation between IL-6 levels and the MG Composite score, indicating that higher levels of IL-6 were associated with better control of the disease. CONCLUSION: This exploratory study suggests that IL-6 is associated with MG clinical status, as assessed by the MGC.

INTRODUÇÃO: A Miastenia Gravis (MG) é uma doença autoimune caracterizada por fraqueza muscular flutuante. OBJETIVOS: avaliar os níveis plasmáticos de citocinas (IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, e IL-17A) em pacientes com MG e controles e investigar se essas citocinas estão associadas com parâmetros clínicos. Este estudo foi conduzido no ambulatório de doenças neuromusculares do Hospital das Clínicas, Universidade Federal de Minas Gerais (UFMG), Brasil. MÉTODOS: Foi coletado sangue periféricos e os níveis plasmáticos das citocinas foram medidos por citometria em 80 pacientes com MG tratados e em 50 controles. O MG composite (MGC) foi utilizado para avaliar a fraqueza muscular e a gravidade dos sintomas motores típicos da MG. RESULTADOS: Os pacientes com MG em tratamento apresentaram menores níveis de todas as citocinas avaliadas comparados ao controle. Houve uma correlação negativa entre os níveis de IL-6 e o MGC, indicando que altos níveis de IL-6 estão associados com melhor controle da doença. CONCLUSÃO: este estudo exploratório sugere que a IL-6 está associada com o status clínico da MG, quando avaliado pelo MGC.

Association of an expanded inflammatory mediators response with clinical and laboratory data in the postoperative period of pulmonary resection: a prospective clinical study / Associação de perfil ampliado dos mediadores da resposta inflamatória com dados clínicos e laboratoriais no período pós-operatório de ressecção pulmonar: estudo clínico prospectivo

ABSTRACT Introduction: patients undergoing pulmonary resection may experience local or remote complications in the postoperative period due to the inflammatory response, which increases the length of hospital stay and costs. This study objective was to establish an expanded interleukins profile, identifying the main actors in the postoperative inflammatory response, and to correlate them with clinical and laboratory data of patients submitted to pulmonary resection. Methods: this was a prospective, interventional, longitudinal study of 27 cases of pulmonary resection performed at HC-UNICAMP, in which we analyzed serum levels of IL 1 α, IL 1 β, IL 1 ra, IL 2, IL 13, IL 6, IL 8, IL 10, IL 12 (p40), IL 12 (p70), IL 17a, TNF α, TNF β, IFN γ, TGF β, MIP 1α, MIP 1β, MCP 1, MCP 3, VEGF, and clinical data before, during, and after surgery. Results: Individuals had a median age of 63 years, 16 (59%) being male and 11 (41%), female. The clinical factors that influenced inflammatory response were body mass index, smoking, and previous use of corticosteroids, while the influencing laboratory data were the numbers of leukocytes and platelets. Discussion: within this expanded interleukin profile in the inflammatory response of lung resections, our study showed that interleukins IL 6, IL 8, IL 10, IL 1 β, and TNF α should be considered for assessing humoral inflammation. Conclusion: this study can aid in the identification of clinical or pharmacological interventions that modulate the inflammatory response in the perioperative period of pulmonary resections, mitigating local and systemic complications.

RESUMO Introdução: pacientes submetidos a ressecção pulmonar podem apresentar complicações locais ou remotas no pós-operatório decorrente da resposta inflamatória, que aumenta o tempo de internação e de custos hospitalares. O objetivo deste trabalho foi estabelecer perfil ampliado do comportamento das interleucinas, identificar as principais interleucinas que atuam na resposta inflamatória no período pós-operatório e associá-las com dados clínicos e laboratoriais dos pacientes submetidos a ressecção pulmonar. Métodos: Estudo prospectivo com 27 casos de ressecção pulmonar realizados no HC-UNICAMP. Foram analisados níveis séricos de IL-1 α, IL-1 β, IL-1 ra, IL-2, IL-13, IL-6, IL-8, IL-10, IL-12 (p40), IL-12 (p70), IL-17a, TNF- α, TNF- β, IFN-γ, TGF- β, MIP-1 α, MIP-1 β, MCP-1, MCP-3, VEGF e dados clínicos antes, durante e após a operação. Resultados: indivíduos apresentaram mediana de idade de 63 anos, sendo 16 (59%) do sexo masculino e 11 (41%) do sexo feminino. Os fatores clínicos que influenciam na resposta inflamatória são: índice de massa corporal, tabagismo e uso prévio de corticóide, enquanto que os dados laboratoriais se expressam nos números de leucócitos e plaquetas. Discussão: dentro deste ampliado perfil das interleucinas na resposta inflamatória das ressecções pulmonares, este estudo mostrou que devem ser valorizadas para avaliar inflamação humoral as interleucinas: IL-6, IL-8, IL-10, IL-1 β e TNF- α. Conclusão: este estudo pode colaborar na identificação de intervenções clínicas ou farmacológicas que modulem a resposta inflamatória no período peri-operatório das ressecções pulmonares, mitigando as complicações locais e sistêmicas.

Meso-scale Discovery Assay Detects the Changes of Plasma Cytokine Levels in Mice after Low or High LET Ionizing Irradiation / 生物医学与环境科学（英文）

Objective@#To obtain precise data on the changes in the levels of 29 cytokines in mice after high or low linear energy transfer (LET) irradiation and to develop an accurate model of radiation exposure based on the cytokine levels after irradiation.@*Methods@#Plasma samples harvested from mice at different time points after carbon-ion or X-ray irradiation were analyzed using meso-scale discovery (MSD), a high-throughput and sensitive electrochemiluminescence measurement technique. Dose estimation equations were set up using multiple linear regression analysis.@*Results@#The relative levels of IL-6 at 1 h, IL-5 and IL-6 at 24 h, and IL-5, IL-6 and IL-15 at 7 d after irradiation with two intensities increased dose-dependently. The minimum measured levels of IL-5, IL-6 and IL-15 were up to 4.0076 pg/mL, 16.4538 pg/mL and 0.4150 pg/mL, respectively. In addition, dose estimation models were established and verified.@*Conclusions@#The MSD assay can provide more accurate data regarding the changes in the levels of the cytokines IL-5, IL-6 and IL-15. These cytokines could meet the essential criteria for radiosensitive biomarkers and can be used as radiation indicators. Our prediction models can conveniently and accurately estimate the exposure dose in irradiated organism.

Changes in the Cytokine Profiles of Patients with Chronic Hepatitis B during Antiviral Therapy / 生物医学与环境科学（英文）

Objective@#To investigate the changes in the cytokine profiles of chronic hepatitis B (CHB) patients undergoing antiviral treatment.@*Methods@#Hepatitis B e antigen (HBeAg)-positive patients were treated with Pegylated interferon (PEG-IFN) and entecavir (ETV). Clinical biochemistry and cytokines were detected at baseline and every 3 months.@*Results@#In all, 200 patients completed 48 weeks of treatment, 100 in the PEG-IFN group and 100 in the ETV group. During 3-6 months of treatment, compared with baseline, the PEG-IFN group showed a significant decrease in interferon-gamma (IFN-γ), interleukin-17A (IL-17A), interleukin-6(IL-6), interleukin-10(IL-10), and transforming growth factor beta (TGF-β) ( @*Conclusion@#During antiviral therapy, a change in the cytokine profile occurred; in the aspect of immune control and functional cure, PEG-IFN was significantly better than ETV.

Effect of coinfection with influenza virus and bacteria on host damage / Efecto de la coinfección por virus de la influenza y bacterias en el daño al hospedero

Abstract Background: Influenza virus infection is often complicated by a bacterial infection, with this coinfection causing severe pneumonia. If not timely treated, the disease can cause death. Objective: To demonstrate, in animal models, that coinfection with influenza virus and bacteria that affect the respiratory tract causes multisystemic damage. Method: Six groups of mice were formed: a control group, one infected with the influenza virus, two infected with bacteria: Haemophilus influenzae and Streptococcus pneumoniae, respectively; and two co-infected with influenza virus and Haemophilus influenzae or Streptococcus pneumoniae, respectively. Results: Of the six groups of mice, only the group co-infected with influenza virus and Streptococcus pneumoniae showed damage to thoracic and abdominal organs. A decrease in serum cytokine levels was found in all study groups, which was more pronounced in the co-infected mice. Conclusions: The groups of mice infected with Streptococcus pneumoniae or influenza virus alone showed no damage, which indicates that coexistence of these infections caused the damage in the group of co-infected mice.

Resumen Antecedentes: La infección por el virus de la influenza con frecuencia se complica con una infección bacteriana, coinfección que provoca cuadros graves de neumonía, la cual puede ocasionar la muerte si no es tratada en forma oportuna. Objetivo: Demostrar en modelos animales que la coinfección por el virus de la influenza y bacterias que afectan el tracto respiratorio ocasiona daño multisistémico. Método: Se formaron seis grupos de ratones: un grupo control, uno infectado de virus de la influenza, dos infectados de bacterias: Haemophilus influenzae y Streptococcus pneumoniae, respectivamente; y dos coinfectados de virus de la influenza y Haemophilus influenzae y Streptococcus pneumoniae, respectivamente. Resultados: De los seis grupos de ratones, solo en el grupo coinfectado de virus de la influenza y Streptococcus pneumoniae se observó daño en órganos torácicos y abdominales. En todos los grupos se encontró disminución de los niveles séricos de las citocinas, mayor en los ratones coinfectados. Conclusiones: Los grupos de ratones infectados solo de Streptococcus pneumoniae o el virus de la influenza no presentaron daños, lo cual indica que la coexistencia de estas infecciones fue la que ocasionó el daño en el grupo de ratones coinfectados.

Respuesta de las citocinas a la combinación de simbióticos y lactoferrina en recién nacidos de muy bajo peso al nacer: ensayo controlado aleatorizado / Cytokine responses to symbiotic and lactoferrin combination in very low birth weight neonates: a randomized control trial

Introducción. Los probióticos y prebióticos presentan beneficios potenciales en la inflamacióncrónica de las mucosas, incluida la prevención de la enterocolitis necrosante. No obstante, los mecanismos y resultados de estos efectos inmunomoduladores son confusos. El objetivo fue investigar la respuesta de las citocinas a Lactobacillus y Bifidobacterium asociados con fructo- y galactooligosacáridos (simbióticos) y lactoferrina en recién nacidos de muy bajo peso al nacer.Población y métodos. Se asignó aleatoriamente a lactantes con ≤32 semanas de gestación y ≤1500 g de peso para recibir simbióticos o 1 ml de agua destilada como placebo desde la primera alimentación hasta el alta. Se obtuvieron muestras de sangre los días posnatales 0 ± 2, 14 ± 2 y 28 ± 2, y se midieron interferón-γ, interleucina (IL)-5, IL-10 e IL-17A.Resultados. En el grupo del estudio (n = 25), la concentración de IL-10 disminuyó a lo largo del estudio (p = 0,011), pero no cambió en el grupo de referencia. La concentración de IL-5 se mantuvo constante los primeros 14 días y luego disminuyó significativamente (p= 0,042) en el grupo del estudio, mientras que aumentó en los primeros 14 días (p = 0,019) y luego disminuyó en 28 días (p = 0,011) en el grupo de referencia (n = 25).La concentración de otras citocinas no cambió a lo largo del estudio.Conclusión. El uso combinado de probióticos con oligosacáridos y lactoferrina estuvo asociado con una disminución en la concentración de IL-10, pero no se observó un cambio en las otras citocinas.

Introduction. Probiotics and prebiotics, which are multifunctional agents, have potential benefits in chronic mucosal inflammation, including the prevention of necrotizing enterocolitis. However, the mechanisms and the results of these immunomodulatory effects are not clear. This study aimed to investigate the cytokine response to the combination of Lactobacillus and Bifidobacterium together with fructo- and galacto-oligosaccharides (symbiotic) and lactoferrin in very low birth weight neonates.Population and Methods. Infants ≤ 32 GWs and ≤ 1,500 g were randomly assigned to receive a symbiotic combination or 1 ml distilled water as placebo starting with the first feed until discharge. Blood samples were obtained at postnatal 0 ± 2, 14 ± 2, and 28 ± 2 days, and the serum levels of interferon-γ, interleukin (IL)-5, IL-10, and IL-17A were measured.Results. In the study group (n = 25), the IL-10 levels decreased throughout the study period (p = 0.011) but did not change in the control group. The IL-5 levels remained steady in the first 14 days and decreased significantly thereafter (p = 0.042) in the study group, whereas they increased in the first 14 days (p = 0.019), and then decreased in 28 days (p = 0.011) in the control group (n = 25). The levels of the other cytokines did not change throughout the study period.Conclusion.The combined use of probiotics with oligosaccharides and lactoferrin was associated with a decrease in IL-10 levels, but no change was observed in the other cytokines.

Rhoifolin regulates oxidative stress and proinflammatory cytokine levels in Freund's adjuvant-induced rheumatoid arthritis via inhibition of NF-κB

Rheumatoid arthritis (RA) is an autoimmune disease of knee joints involving pain and inflammation. Rhoifolin is a plant flavonoid known to have antioxidant and anti-inflammatory properties. This study was taken to identify the effect of rhoifolin on complete Freund's adjuvant (CFA)-induced arthritis in the rat model. Treatment with rhoifolin (10 and 20 mg/kg) showed a significant improvement in the overall health parameters such as paw edema and weight loss. This improvement in morphological parameters corroborated the findings with gross morphological changes observed in the histopathological analysis. Rhoifolin treatment also caused a significant decrease in oxidative stress, evident from changes in intracellular levels of glutathione, glutathione peroxidase, malondialdehyde, and superoxide dismutase in the articular cartilage tissue. Moreover, proinflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin(IL)-1β, and IL-6 showed a significant downregulation of gene expression and intracellular protein concentration levels. The NF-κB pathway showed a significant attenuation as evident in the significant reduction in the levels of NF-κB p65 and p-IκB-α. These results indicated that rhoifolin can be a natural therapeutic alternative to the extant regimens, which include non-steroidal anti-inflammatory drugs and immunosuppressants. Additionally, the antioxidant and anti-inflammatory action of rhoifolin was probably mediated by the NF-κB pathway. However, the exact target molecules of this pathway need to be determined in further studies.

Ibuprofen increases the serum Omentin levels in rats after abdominal surgery

SUMMARY AIMS Omentin is an adipokine primarily produced by visceral adipose tissue and its reduced levels have been shown to be associate with worse metabolic outcomes. We aimed to study the effects of preoperative ibuprofen on postoperative omentin levels in rats after surgery. METHODS Forty-eight albino Wistar rats, 6 in each of 8 groups according to the surgical procedure (laparotomy, laparotomy plus ibuprofen (IBU), nephrectomy, nephrectomy plus IBU, hepatectomy, hepatectomy plus IBU, splenectomy and splenectomy plus IBU). The Omentin levels of the groups were postoperatively analyzed. RESULTS The mean omentin was significantly higher in the laparotomy plus IBU group compared to the laparotomy group (p<0.001). Mean Omentin was significantly higher in the hepatectomy plus IBU group compared to the hepatectomy group (p=0.01). Mean Omentin was significantly higher in the nephrectomy plus IBU group compared to the nephrectomy group (p=0.001). CONCLUSION We suggest that preoperative ibuprofen may enhance circulating levels of Omentin, which has beneficial effects in trauma and inflammation settings in subjects that undergo minor or major abdominal surgery.

RESUMO OBJETIVOS A omentina é uma adipocina produzida principalmente pelo tecido adiposo visceral e níveis reduzidos dela foram associados a piores desfechos metabólicos. Nosso objetivo foi estudar os efeitos do uso pré-operatório do ibuprofeno nos níveis pós-operatórios da omentina em ratos. METODOLOGIA Quarenta e oito ratos Wistar albinos foram divididos em 8 grupos (6 em cada), de acordo com o procedimento cirúrgico: laparotomia, laparotomia e ibuprofeno (IBU), nefrectomia, nefrectomia e IBU, hepatectomia, hepatectomia e IBU, esplenectomia, e esplenectomia e IBU. Os níveis de omentina dos grupos foram analisados após a cirurgia. RESULTADOS A omentina média foi significativamente maior no grupo de laparotomia e IBU do que no grupo de laparotomia (p<0,001). A omentina média foi significativamente maior no grupo de hepatectomia e IBU do que no grupo de hepatectomia (p = 0,01). A omentina média foi significativamente maior no grupo de nefrectomia e IBU do que no grupo de nefrectomia (p = 0,001). CONCLUSÃO Sugerimos que o uso pré-operatório de ibuprofeno pode aumentar os níveis circulantes de omentina, que têm efeitos benéficos em um contexto de trauma e inflamação em indivíduos submetidos cirurgia abdominal.

Hypoxia inducible factor-1 (HIF-1α) reduced inflammation in spinal cord injury via miR-380-3p/ NLRP3 by Circ 0001723

BACKGROUND: Spinal cord injury (SCI) is a severe central nervous system trauma. The present study aimed to evaluate the effect of HIF-1α on inflammation in spinal cord injury (SCI) to uncover the molecular mechanisms of anti-inflammation. RESULTS: HIF-1α was reduced in SCI model rats and HIF-1α activation reduced TNF-α, IL-1ß, IL-6 and IL-18 levels in SCI model rats. Meanwhile, Circ 0001723 expression was down-regulated and miR-380-3p expression was up-regulated in SCI model rats. In vitro model, down-regulation of Circ 0001723 promoted TNF-α, IL-1ß, IL-6 and IL-18 levels, compared with control negative group. However, over-expression of Circ 0001723 reduced TNF-α, IL-1ß, IL-6 and IL-18 levels in vitro model. Down-regulation of Circ 0001723 suppressed HIF-1α protein expressions and induced NLRP3 and Caspase-1 protein expressions in vitro model by up-regulation of miR-380-3p. Next, inactivation of HIF-1α reduced the pro-inflammation effects of Circ 0001723 in vitro model. Then, si-NLRP3 also inhibited the pro-inflammation effects of Circ 0001723 in vitro model via promotion of autophagy. CONCLUSIONS: We concluded that HIF-1α reduced inflammation in spinal cord injury via miR-380-3p/ NLRP3 by Circ 0001723.

Acute Strength Exercise Decreases Satiety by Modifying Blood Cytokines Levels in Physically Active Men

Abstract Aim: Exercise elicits adaptations in several physiological systems, such as the gastrointestinal tract. We evaluated the effects of an acute strength exercise (acute-SE) on gastric satiety and its correlation with creatinine kinase (CK), lactate, and plasma cytokine levels in humans. Methods: Anthropometric parameters, body composition, muscular strength, and satiety (drink test protocol) at rest and exercise were assessed. Results: In the squat, bench press, and T-bar row exercises, we observed a significant decrease (p<0.05) in muscular strength in the second, third, and fourth sets compared with that in the first set. Compared with rest, we observed a significant increase (p<0.05) in CK and lactate levels after acute-SE. In the drink test, acute-SE significantly increased (p <0.05) the total intake, calories ingested, and a total time of ingestion. Concerning cytokines, there was a significant increase (p<0.05) after acute-SE of IL-1β and IL-6 levels at the beginning of the test and a decrease in IL-6, -10, -13, and TNF-α levels after acute-SE at the end of the test (p<0.05). There was a correlation between CK, lactate, and total intake after acute-SE (p<0.05) as well as between IL-6, 13, TNF-α, and volume ingested in the last score of the drink test after acute-SE (p<0.05). Conclusion: Acute-SE decreases satiety associated with changes in lactate, CK, and plasma cytokine levels in healthy humans.

Acute effect of passive cycle-ergometry and functional electrical stimulation on nitrosative stress and inflammatory cytokines in mechanically ventilated critically ill patients: a randomized controlled trial

Early mobilization is beneficial for critically ill patients because it reduces muscle weakness acquired in intensive care units. The objective of this study was to assess the effect of functional electrical stimulation (FES) and passive cycle ergometry (PCE) on the nitrous stress and inflammatory cytometry in critically ill patients. This was a controlled, randomized, open clinical trial carried out in a 16-bed intensive care unit. The patients were randomized into four groups: Control group (n=10), did not undergo any therapeutic intervention during the study; PCE group (n=9), lower-limb PCE for 30 cycles/min for 20 min; FES group (n=9), electrical stimulation of quadriceps muscle for 20 min; and FES with PCE group (n=7), patients underwent PCE and FES, with their order determined randomly. The serum levels of nitric oxide, tumor necrosis factor alpha, interferon gamma, and interleukins 6 and 10 were analyzed before and after the intervention. There were no differences in clinical or demographic characteristics between the groups. The results revealed reduced nitric oxide concentrations one hour after using PCE (P<0.001) and FES (P<0.05), thereby indicating that these therapies may reduce cellular nitrosative stress when applied separately. Tumor necrosis factor alpha levels were reduced after the PCE intervention (P=0.049). PCE and FES reduced nitric oxide levels, demonstrating beneficial effects on the reduction of nitrosative stress. PCE was the only treatment that reduced the tumor necrosis factor alpha concentration.

Biochanin A attenuates myocardial ischemia/reperfusion injury through the TLR4/NF-κB/NLRP3 signaling pathway

Abstract Purpose: Myocardial ischemia/reperfusion (Ml/R) injury is a leading cause of damage in cardiac tissues, with high rates of mortality and disability. Biochanin A (BCA) is a main constituent of Trifolium pratense L. This study was intended to explore the effect of BCA on Ml/R injury and explore the potential mechanism. Methods: In vivo MI/R injury was established by transient coronary ligation in Sprague-Dawley rats. Triphenyltetrazolium chloride staining (TTC) was used to measure myocardial infarct size. ELISA assay was employed to evaluate the levels of myocardial enzyme and inflammatory cytokines. Western blot assay was conducted to detect related protein levels in myocardial tissues. Results: BCA significantly ameliorated myocardial infarction area, reduced the release of myocardial enzyme levels including aspartate transaminase (AST), creatine kinase (CK-MB) and lactic dehydrogenase (LDH). It also decreased the production of inflammatory cytokines (IL-1β, IL-18, IL-6 and TNF-α) in serum of Ml/R rats. Further mechanism studies demonstrated that BCA inhibited inflammatory reaction through blocking TLR4/NF-kB/NLRP3 signaling pathway. Conclusion: The present study is the first evidence demonstrating that BCA attenuated Ml/R injury through suppressing TLR4/NF-kB/NLRP3 signaling pathway-mediated anti-inflammation pathway.

Effects of lithium on inflammatory and neurotrophic factors after an immune challenge in a lisdexamfetamine animal model of mania

Objective: To evaluate whether an animal model of mania induced by lisdexamfetamine dimesylate (LDX) has an inflammatory profile and whether immune activation by lipopolysaccharides (LPS) has a cumulative effect on subsequent stimuli in this model. We also evaluated the action of lithium (Li) on inflammatory and neurotrophic factors. Methods: Adult male Wistar rats were subjected to an animal model of mania. After the open-field test, they were given LPS to induce systemic immune activation. Subsequently, the animals' blood was collected, and their serum levels of brain-derived neurotrophic factor and inflammatory markers (tumor necrosis factor [TNF]-α, interleukin [IL]-6, IL-1β, IL-10, and inducible nitric oxide synthase [iNOS]) were measured. Results: LDX induced hyperactivity in the animals, but no inflammatory marker levels increased except brain-derived neurotrophic factor (BDNF). Li had no effect on serum BDNF levels but prevented iNOS levels from increasing in animals subjected to immune activation. Conclusion: Although Li prevented an LPS-induced increase in serum iNOS levels, its potential anti-inflammatory effects in this animal model of mania were conflicting.

Lipopolysaccharide-stimulated intracellular cytokines and depressive symptoms in community-dwelling older adults

Abstract Background Inflammation is involved in the pathophysiology of depression, and circulating inflammatory cytokines have been associated with depressive symptoms. However, measuring circulating cytokines have inherent methodological limitations. In vitro lipopolysaccharide (LPS)-stimulated intracellular cytokines (ICCs) overcome these limitations. Furthermore, because psychosocial and physiological stressors activate inflammatory responses and LPS-stimulated ICCs reflect the inflammatory responsivity of monocytes to such stressors, ICCs may reflect individual stress responsivity. Methods This cross-sectional study examined whether LPS-stimulated expression of ICCs in peripheral blood mononuclear cells (PBMCs) is a sensitive inflammation measure correlated with depressive symptoms in 180 community-dwelling older adults. We tested correlations of not only intracellular but also circulating inflammatory markers with depressive symptoms assessed using the 10-item Center for Epidemiological Studies Depression Scale (CES-D). Intracellular markers included expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and both in PBMCs. Circulating markers included IL-6, TNF-α, and C-reactive protein (CRP) in plasma. Results None of the correlations were statistically significant. However, in contrast to circulating markers, the correlations of ICCs were consistently in the expected direction, i.e., higher ICC expression correlating with higher depression severity. Discussion Despite the non-significant findings, further research is required for the evaluation of LPS-stimulated ICC expression as biomarkers of depressive symptoms.

Niveles Plasmáticos de Citoquinas Proinflamatorias en Cáncer de Próstata / Serum levels of proinflammatory cytokines in prostate cancer

INTRODUCTION: Prostate cancer has become an important public health problem affecting millions of men worldwide every year. Like other malignant tumors, prostate cancer shows evidence of a strong inflammatory component that is dependent on the release of pro-inflammatory cytokines, which might play a major role in the development and progression of the tumor, helping in its early stage, progression and aggressiveness. AIMS: The goal of this study was to determine the relationships between the serum levels of pro-inflammatory cytokines and the different stages of prostate cancer. To this end, sera from patients enrolled by The Laboratory of Metabolic Diseases and Cancer of the Faculty of Pharmacy and Biochemistry at the University Juan Agustín Maza in Argentina, were analyzed through ELISA and their pro-inflammatory cytokines (IL-6, TNF-α and MCP-1) quantified. Patients were first classified into three groups (Control, at Risk, and Cancer subjects) and anthropometric, biochemical and histological parameters of prostate were then determined for all groups. RESULTS AND CONCLUSIONS: Despite displaying elevated serum concentrations of IL-6 and TNF-α in the Cancer and the Risk groups compared to the Control group, the differences did not reach significance. However, there was a positive correlation between these cytokines only in the Risk and Cancer groups, showing a general inflammatory behavior in these patients. The results obtained provide general data about the behavior of pro-inflammatory cytokines in prostate cancer. However, they do not demonstrate a direct correlation between serum levels and neoplastic progression. Nevertheless, these findings do not rule out a possible relationship between prostate cancer and serum levels of pro-inflammatory cytokines.

Relationship of T lymphocytes, cytokines, immunoglobulin E and nitric oxide with otitis media with effusion in children and their clinical significances

SUMMARY OBJECTIVE To investigate the relations of T lymphocytes, cytokines, immunoglobulin E, and nitric oxide with otitis media with effusion (OME) in children and their clinical significances. METHODS Fifty children with OME treated in our hospital were enrolled in the study (observation group). Fifty healthy children were selected as control. The percentages of CD4+ and CD8+ T lymphocyte and CD4+/CD8+ ratio in peripheral blood, and the levels of cytokine (IL)-2, IL-4, IL-6, immunoglobulin E (IgE) and nitric oxide (NO) in peripheral blood and middle ear effusion (MEE) in both groups were detected. The correlations of these indexes with OME were analyzed. RESULTS The percentage of peripheral blood CD4+ and CD8+ levels, CD4+/CD8 ratio, IgE, and NO levels in the observation group were significantly higher than those in the control group (P < 0.01). In the observation group, the IL-2 and IL-6 levels, and IgE and NO levels in the MEE were significantly higher than those in peripheral blood (P < 0.01). In addition, in the observation group, the MEE IL-2 and IL-6 levels were positively correlated with peripheral blood CD4+/CD8+ ratio, respectively r = 0.366, P = 0.009; r = 0.334, P = 0.018. CONCLUSIONS The levels of peripheral blood CD4+ and CD8+ lymphocytes and MEE IL-2, IL-6, IgE, and NO levels are increased in children with OME. These indexes have provided significant clues for the diagnosis of OME in children.

RESUMO OBJETIVO Investigar as relações entre linfócitos T, citocinas, imunoglobulina E e óxido nítrico e a otite média com efusão (OME) em crianças e sua significância clínica. MÉTODOS Cinquenta crianças com OME tratadas em nosso hospital foram incluídas no estudo (grupo de observação). Selecionamos também 50 crianças saudáveis como controle. As porcentagens de linfócitos T CD4 + e CD8 + e a razão CD4+/CD8+ no sangue periférico, além dos níveis das citocinas IL-2, IL-4, IL-6, imunoglobulina E (IgE) e óxido nítrico (NO) no sangue periférico e de efusão no ouvido médio (MEE) de ambos os grupos foram medidos. A correlação desses índices com a OME foi analisada. RESULTADOS A porcentagem dos níveis de CD4+ e CD8 +, da razão CD4+/CD8+, de IgE e NO no sangue periférico do grupo de observação foram significativamente maiores do que no grupo controle (P < 0,01). No grupo de observação, os níveis de IL-2 e IL-6, IgE e NO em MEE foram significativamente maiores do que no sangue periférico (P < 0,01). Além disso, no grupo de observação, foi encontrada uma correlação positiva entre os níveis de IL-2 e IL-6 em MEE e a razão de CD4+/CD8+no sangue periférico, respectivamente, r = 0,366, P = 0,009; r = 0,334, P = 0,018. CONCLUSÃO Os níveis de linfócitos CD4 + e CD8 + no sangue periférico e IL-2, IL-6, IgE e NO em MEE são mais altos em crianças com OME. Esses índices forneceram evidências valiosas para o diagnóstico de OME em crianças.

Predictive value of plasma cytokines for acute kidney injury following lung resection surgery: prospective observational study / Valor preditivo das citocinas plasmáticas para lesão renal aguda após cirurgia de ressecção pulmonar: estudo observacional prospectivo

Abstract Background and objectives: Patients undergoing lung resection surgery are at risk of developing postoperative acute kidney injury. Determination of cytokine levels allows the detection of an early inflammatory response. We investigated any temporal relationship among perioperative inflammatory status and development of acute kidney injury after lung resection surgery. Furthermore, we evaluated the impact of acute kidney injury on outcome and analyzed the feasibility of cytokines to predict acute kidney injury. Methods: We prospectively analyzed 174 patients scheduled for elective lung resection surgery with intra-operative periods of one-lung ventilation periods. Fiberoptic broncho-alveolar lavage was performed in each lung before and after one-lung ventilation periods for cytokine analysis. As well, cytokine levels were measured from arterial blood samples at five time points. acute kidney injury was diagnosed within 48 h of surgery based on acute kidney injury criteria. We analyzed the association between acute kidney injury and cardiopulmonary complications, length of intensive care unit and hospital stays, intensive care unit re-admission, and short-term and long-term mortality. Results: The incidence of acute kidney injury in our study was 6.9% (12/174). Acute kidney injury patients showed higher plasma cytokine levels after surgery but differences in alveolar cytokines were not detected. Although no patient required renal replacement therapy, acute kidney injury patients had higher incidence of cardiopulmonary complications and increased overall mortality. Plasma interleukin-6 at 6 h was the most predictive cytokine of acute kidney injury (cut-off point at 4.89 pg.mL-1). Conclusions: Increased postoperative plasma cytokine levels are associated with acute kidney injury after lung resection surgery in our study, which worsens the prognosis. Plasma interleukin-6 may be used as an early indicator for patients at risk of developing acute kidney injury after lung resection surgery.

Resumo Justificativa e objetivos: Os pacientes submetidos à cirurgia de ressecção pulmonar apresentam risco de desenvolver lesão renal aguda pós-operatória. A determinação dos níveis de citocinas permite detectar uma resposta inflamatória precoce. Investigamos a relação temporal entre o estado inflamatório perioperatório e o desenvolvimento de lesão renal aguda após cirurgia de ressecção pulmonar. Além disso, avaliamos o impacto da lesão renal aguda no desfecho e analisamos a viabilidade das citocinas para prever este tipo de lesão. Métodos: No total, foram analisados prospectivamente 174 pacientes agendados para cirurgia eletiva de ressecção pulmonar com períodos intraoperatórios de ventilação monopulmonar. Lavado bronco-alveolar com fibra óptica foi realizado em cada pulmão antes e após os períodos de ventilação monopulmonar para análise das citocinas. Os níveis de citocina foram medidos a partir de amostras de sangue arterial em cinco momentos. A lesão renal aguda foi diagnosticada dentro de 48 horas após a cirurgia, com base nos critérios para sua verificação. Analisamos a associação entre lesão renal aguda e complicações cardiopulmonares, tempo de internação em unidade de terapia intensiva e de internação hospitalar, reinternação em unidade de terapia intensiva e mortalidade a curto e longo prazos. Resultados: A incidência de lesão renal aguda no estudo foi de 6,9% (12/174). Os pacientes com lesão renal aguda apresentaram níveis mais altos de citocinas plasmáticas após a cirurgia, mas não foram detectadas diferenças nas citocinas alveolares. Embora nenhum paciente tenha precisado de terapia renal substitutiva, os com lesão renal aguda apresentaram maior incidência de complicações cardiopulmonares e aumento da mortalidade geral. A interleucina-6 plasmática em seis horas foi a citocina mais preditiva de lesão renal aguda (ponto de corte em 4,89 pg.mL-1). Conclusões: O aumento dos níveis plasmáticos de citocinas no pós-operatório está associado à lesão renal aguda após cirurgia de ressecção pulmonar no estudo, o que piora o prognóstico. A interleucina-6 plasmática pode ser usada como um indicador precoce para pacientes com risco de desenvolver lesão renal aguda após cirurgia de ressecção pulmonar.

A Proposed Inflammatory Score of Circulating Cytokines/Adipokines Associated with Resistant Hypertension, but Dependent on Obesity Parameters / Proposta de um Escore Inflamatório de Citocinas e Adipocinas Plasmáticas Associado à Hipertensão Resistente, mas Dependente dos Parâmetros de Obesidade

Abstract Background: There is evidence that subclinical systemic inflammation is present in resistant hypertension (RHTN). Objective: The aim of the study was to develop an integrated measure of circulating cytokines/adipokines involved in the pathophysiology of RHTN. Methods: RHTN (n = 112) and mild to moderate hypertensive (HTN) subjects (n=112) were studied in a cross-sectional design. Plasma cytokines/adipokines (TNF-alpha, interleukins [IL]-6, -8, -10, leptin and adiponectin) values were divided into tertiles, to which a score ranging from 1 (lowest tertile) to 3 (highest tertile) was assigned. The inflammatory score (IS) of each subject was the sum of each pro-inflammatory cytokine scores from which anti-inflammatory cytokines (adiponectin and IL-10) scores were subtracted. The level of significance accepted was alpha = 0.05. Results: IS was higher in RHTN subjects compared with HTN subjects [4 (2-6) vs. 3 (2-5); p = 0.02, respectively]. IS positively correlated with body fat parameters, such as body mass index (r = 0.40; p < 0.001), waist circumference (r = 0.30; p < 0.001) and fat mass assessed by bioelectrical impedance analysis (r = 0.31; p < 0.001) in all hypertensive subjects. Logistic regression analyses revealed that IS was an independent predictor of RHTN (OR = 1.20; p = 0.02), independent of age, gender and race, although it did not remain significant after adjustment for body fat parameters. Conclusion: A state of subclinical inflammation defined by an IS including TNF-alpha, IL-6, IL-8, IL-10, leptin and adiponectin is associated with obese RHTN. In addition, this score correlates with obesity parameters, independently of hypertensive status. The IS may be used for the evaluation of conditions involving low-grade inflammation, such as obesity-related RHTN. Indeed, it also highlights the strong relationship between obesity and inflammatory process.

Resumo Fundamento: Evidências indicam que a inflamação sistêmica subclínica está presente na hipertensão arterial resistente (HAR). Objetivo: Desenvolver uma medida que integra citocinas envolvidas na fisiopatologia da HAR. Métodos: Indivíduos com HAR (n = 112) e indivíduos com hipertensão leve a moderada (HT) (n = 112) foram estudados em delineamento transversal. Valores de citocinas/adipocinas plasmáticas [TNF-alfa, interleucinas (IL)-6, -8, -10, leptina e adiponectina] foram divididos em tercis, e lhes atribuído um escore variando de 1 (tercil mais baixo) a 3 (tercil mais alto). O escore inflamatório (EI) de cada participante foi calculado como a soma do escore de cada citocina pró-inflamatória da qual subtraiu-se o escore de cada citocina anti-inflamatória (adiponectina e IL-10). O nível de significância aceito foi alfa = 0,05. Resultados: O EI foi mais alto nos indivíduos com HAR em comparação a indivíduos com HT [4 (2-6) vs. 3 (2-5); p = 0,02, respectivamente]. O EI correlacionou-se positivamente com parâmetros de gordura corporal, tais como índice de massa corporal (r = 0,40; p < 0,001), circunferência da cintura (r = 0,30; p < 0,001) e massa gorda avaliada por bioimpedância (r = 0,31; p < 0,001) em todos os indivíduos hipertensos. Análises de regressão logística mostraram que o EI foi um preditor independente de HAR (OR = 1,20; p = 0,02), independentemente de idade, sexo e raça; porém, o modelo perdeu significância estatística após ajuste para os parâmetros de gordura corporal. Conclusão: Um estado de inflamação subclínica definida pelo EI incluindo TNF-alfa, IL-6, IL-8, IL-10, leptina e adiponectina está associado com indivíduos obesos com HAR. Além disso, o escore correlaciona-se com parâmetros de obesidade, independentemente do grau de hipertensão. O EI pode ser usado na avaliação de condições que envolvem inflamação subclínica, tal como HAR relacionada à obesidade. O estudo também destaca a forte relação entre obesidade e inflamação.