Abstract The incidence of adverse cardiovascular events is higher among spectators of exciting sports events, particularly in patients with coronary artery disease (CAD), but the mechanistic link between the events is not known. We assessed the hemodynamic, autonomic function, plasma catecholamines, endothelin-1, interleukin-6, and markers of platelet activation and blood coagulation of enthusiastic male ice hockey spectators with CAD (n=55, 60±9 years) and healthy subjects (n=16, 48±6 years) during Finnish national league ice hockey final play-off matches and on a control day. Blood markers were also measured before and after a maximal exercise test with a bicycle ergometer. Systolic and diastolic blood pressure (BP) were significantly higher one hour before, during, and one hour after the match than on the control day. During the match the highest systolic BP was 180±14 vs. 145±15 and diastolic BP was 103±13 vs. 82±11 mmHg (respectively, p<0.001 for both). Heart rate (HR) was higher throughout the match (p<0.05) and remained elevated two hours after the match (p<0001), and measures of HR variability were decreased during the match (p<0.01). Plasma endothelin-1 (ET-1), interleukin-6 (IL-6) and noradrenaline (NOR) increased during the match (p<0.01 for all), but markers of platelet activation and coagulation remained unchanged. ET-1 did not change during exercise but NOR, adrenaline, IL-6, and markers of platelet activation and blood coagulation increased statistically significantly (p<0.0001 for all). A statistically significantly more marked increase in both endothelin-1 and interleukin-6 was observed in CAD patients compared with healthy subjects during the match (time x group interaction p<0.05 for both). The high-frequency power of R-peak-to-R-peak intervals decreased in CAD patients (p<0.001) but did not change in healthy subjects during the match. Maximal metabolic equivalens (METs) were most strongly correlated with ET-1 response during the match (β =-0.45, partial correlation r=-0.43, p=0.002) when age, body mass index, METs, left ventricular ejection fraction, basal ET-1 and subjective experience of excitement were entered into the model as independent variables in a linear stepwise regression analysis. In conclusion, autonomic reactions and vasoconstriction may partly explain the vulnerability to cardiovascular events caused by this type of leisure-time emotional excitement. Emotional excitement causes concomitant increases in markers reflecting vulnerability to atherosclerotic plaque complications, while physical exercise causes more prominent changes in markers of coagulation. Emotional excitement causes more significant increases of markers of vasoconstriction and acute inflammation and withdrawal of cardiac vagal regulation in patients with CAD than in healthy subjects. Exercise capacity may protect against further cardiovascular events in CAD patients because it is associated with reduced ET-1 release during emotional excitement. / Tiivistelmä Jännittävän urheilutapahtuman on havaittu lisäävän sydäntapahtumia erityisesti sepelvaltimotautipotilailla. Syyt eivät ole selvillä. Tutkimuksen kohteena oli jääkiekon mestaruussarjan pudotuspelien seuraamisen vaikutus sekä sepelvaltimotautisten (n=55, 60±9 vuotta) että terveiden (n=16, 48±6 vuotta) jääkiekkofanien verenkiertoon, autonomiseen hermostoon, veren katekolamiinien, endoteliini-1:n (ET-1) ja interleukiini-6:n (IL-6) pitoisuuksiin sekä veren hyytymiseen paikan päällä jäähallissa seurattuna. Muuttujat mitattiin jäähallissa ottelun aikana. Ne mitattiin myös ennen ottelua ja eri päivänä sairaalassa ennen kuntopyörällä tehtyä maksimaalista sydämen kuormitustestiä ja heti sen jälkeen. Sepelvaltimotautipotilaiden ylä- ja alaverenpaineet kohosivat tilastollisesti merkitsevästi tuntia ennen jääkiekkopeliä ja sen aikana, ja ne olivat koholla vielä tunnin ajan pelin jälkeen kontrollipäivään verrattuina. Ottelun aikana yläpaineet olivat 180±14 vs. 145±15 ja alapaineet 103±13 vs. 82±11 mmHg (p<0.001 molemmille painetasoille). Sydämen syke oli korkeampi pelin ajan (p<0.05), ja se pysyi koholla kahden tunnin ajan pelin jälkeen (p<0.001). Lisäksi sykevaihtelu heikentyi pelin aikana (p<0.01) kontrollipäivään verrattuna. Veren ET-1-, IL-6- ja noradrenaliinipitoisuudet (p<0.01) nousivat pelin aikana, mutta veren hyytymistä kuvastavat lukemat säilyivät muuttumattomina. ET-1 ei noussut fyysisessä kuormitustestissä, mutta noradrenaliini- ja adrenaliinipitoisuudet sekä IL-6:n ja veren hyytymistä kuvaavat lukemat kasvoivat tilastollisesti merkitsevästi (p<0.0001). Pelin aikana sepelvaltimotautipotilaiden ET-1 ja IL-6 pitoisuudet kohosivat enemmän kuin terveiden vastaavat arvot (p<0.05). Lisäksi ottelun aikana sydämen sykevaihtelu laski sepelvaltimopotilailla (p<0.001), muttei muuttunut terveillä. Polkupyörätestin maksimaalinen suorituskyky (METs) oli voimakkaasti yhteydessä ET-1 vasteeseen pelin aikana (β =-0.45, r=-0.43, p=0.002), kun ikä, painoindeksi, METs, sydämen supistusvireys, ET-1:n lähtötaso ja koehenkilöiden kokema jännitystaso huomioitiin itsenäisinä muuttujina regressiotyyppisessä tilastolaskennassa. Yhteenvetona todetaan itsenäisesti toimivan hermoston muutosten ja verisuonten supistumisen voivan osittain selittää aiemmin havaitun sydäntapahtumien lisääntymisen tutkimuskohteen tyyppisessä vapaa-ajan tunne-elämyksessä. Jääkiekkopelin jännitys aiheuttaa muutoksia sepelvaltimotautialueiden repeämisherkkyyttä kuvaaviin tekijöihin, kun taas fyysinen rasitus vaikuttaa voimakkaammin veren hyytymistä ilmaiseviin lukemiin. Potilailla jännitys lisäsi enemmän suonten supistuvuutta, akuuttia tulehdusreaktiota ja nosti parasympaattisen hermoston vetäytymistä kuvaavia lukemia terveisiin koehenkilöihin verrattuna. Hyvä suorituskyky voi suojata korkean riskin sepelvaltimotautipotilaita sydäntapahtumilta vähentämällä ET-1:n vapautumista jännityksen aikana.

Thesis (MSc)--Stellenbosch University, 2005. / ENGLISH ABSTRACT: This study (2 x 2 factor design) describes an investigation into the physiological interaction between the peripheral endocrine and cytokine systems after the organism has been exposed to psychological stress. An in vivo rodent model with two interventions was used: (1) mild psychological stress (immobilisation for 2 hours per day, for 4 days); (2) an antiinterleukin (IL)-6-antibody injection. Thirty-nine male Wi star rats were divided into 4 groups and given either the antibody (CA, control antibody) or stress (IP, immobilisation placebo), or both (IA, immobilisation antibody), or neither (CP, control placebo). Antibody and placebo (saline) were injected intraperitoneally. Differences between groups for the following parameters were determined in blood or metabolic tissues, viz. skeletal muscle and liver: 1) corticosterone concentrations, 2) glucocorticoid receptor (GR) binding capacity and 3) activities of metabolic enzymes, tyrosine aminotransferase (TAT) and glutamine synthetase (GS). Groups lP and lA showed a significant loss in body mass (CP vs. lP, p<O.01; CA vs. lA, p<O.001), indicating a main effect of stress. The corticosterone concentrations of only group lP were significantly elevated compared to that of group CP (CP vs. lP, p<O.01), again indicating a main effect of stress. All three intervention groups (CA, lP, lA) had decreased GR binding capacity, with group lA showing a statistically greater decrease (CP vs. CA, p<O.05; IP vs. IA, p<O.01; CP vs. IP, p<O.001; CA vs. IA, p<O.001), indicating main effects of stress and antibody treatment. In groups IP and IA increased activities of both enzymes (TAT and GS) were measured (main effect of stress), with IA again showing the greatest statistically significant increase for both enzymes. The liver tissue displayed greater sensitivity to the stress and antibody regimes. This study provides the first conclusive in vivo evidence for IL-6 modulation of glucocorticoid action in peripheral tissues in response to mild psychological stress. / AFRIKAANSE OPSOMMING: Hierdie studie (met 'n 2 X 2 faktorontwerp) beskryf 'n ondersoek oor die fisiologiese interaksie tussen die perifere endokrien- en sitokiensisteme in organismes blootgestel aan psigologiese stres. Daar word gebruik gemaak van 'n in vivo-rotmodel met twee intervensies: (1) matige psigologiese stres (immobilisering vir 2 uur per dag vir 4 dae); (2) 'n anti-interleukin (IL)-6-antiliggaam inspuiting. Nege-en-dertig manlike Wistar rotte is in vier groepe verdeel en het óf antiliggaam (CA, antiliggaam kontrole), óf stres (IP, immobilisasie placebo), óf beide stres en antiliggaam (lA, immobilisasie antiliggaam) of geen behandeling ontvang (CP, placebo kontrole). Die antiliggaam- en placebo (soutoplossing)- inspuitings is intraperitoneaal toegedien. Verskille tussen die groepe van die volgende parameters, in metaboliese weefsels (skeletspier en lewer), was bepaal: 1) kortikosteroon konsentrasies, 2) glukokortikoïed reseptor (GR) bindingskapasiteit en 3) aktiwiteite van die metaboliese ensieme, tirosien aminotransferase (TAT) en glutamien sintetase (GS). Groepe IP en IA het 'n beduidende afname in gewig getoon (CP vs. IP, p<O.01;CA vs. IA, p<O.001), wat 'n hoof-effek van stres aandui. Die kortikosteroon konsentrasies van slegs IP het beduidend toegeneem in vergelyking met CP (CP vs. IP, p<O.01),wat weereens 'n hoof-effek van stres aandui. AI drie intervensiegroepe (CA, IP, IA) het verlaagte GR bindingskapasiteit getoon, met lA wat 'n groot statistiese afname getoon het (CP vs. CA, p<O.05; IP vs. IA, p<O.01;CP vs. IP, p<O.001;CA vs. IA, p<O.001),wat hoof-effekte van beide stres en antiliggaam-behandeling aandui. In groepe IP and IA is toenames in beide ensiemaktiwiteitvlakke (TAT en GS ensieme) getoon (hoof-effek van stres), met IA wat weereens die grootste toename gewys het. Die lewer het ook verhoogde sensitiwiteit tot die stres- en antiliggaamregimente. Hierdie studie lewer die eerste daadwerklike in vivo bewyse vir IL-6 modulering van glukokortikoïedaksie in perifere weefsels na reaksie op psigologiese stres.

STAT3 is a critical oncogenic transcription factor, but how it becomes aberrantly activated in cancer is unclear. We have discovered a new pathway whose loss is associated with persistent STAT3 activation in human cancer. We found that the tumor suppressor miR-146b is a direct STAT3 target gene in normal breast epithelial cells. However, STAT regulation of miR-146b is subverted in tumor cells and is suppressed by promoter methylation, which is increased in primary breast cancers. Moreover, we show that miR-146b inhibits NF-&#954;B-dependent IL-6 production, IL-6-dependent STAT3 activation, and IL-6/STAT3-driven functional phenotypes, thereby establishing a negative feedback loop. In addition, miR-146b expression appears to be deregulated in tumors with the highest levels of activated STAT3, and is positively correlated with patient survival. Our results indicate a new mechanism of crosstalk between STAT3 and NF-&#954;B relevant to constitutive STAT3 activation in malignancy and the role of inflammation in oncogenesis.

Migraine is one of the most common neurological disorders. The pathological conditions that initiate and sensitize afferent pain signaling are poorly understood. The goal of this study is to identify the ion channels and signaling proteins underlying activation and sensitization of meningeal nociceptors.In trigeminal neurons retrogradely labeled from the cranial meninges, approximately 80% responded to a pH 6.0 application with a rapidly activating and desensitizing ASIC-like current. Pharmacological experiments and kinetics analysis demonstrated that dural afferent pH-sensitive currents were mediated via activation of ASIC3. In addition, applications of decreased pH solutions were able to excite these neurons and generate action potentials. In awake animals, application of decreased pH solutions to the dura produced dose-dependent facial and hindpaw allodynia, which was also mediated through activation of ASIC3. Accumulating evidence indicates that meningeal inflammation induced sensitization of dural afferents contributes to migraine headache. We have demonstrated here that in the presence of mast cell mediators, dural afferents showed a decreased pH threshold and increased activity in response to pH stimuli both in vivo and in vitro. These data provide a cellular mechanism by which decreased pH in the meninges directly excites afferent pain-sensing neurons potentially contributing to migraine headache. It also indicates that inflammatory events within the meninges could sensitize afferent pain signaling and result in increased sensitivity of dural afferents.Intracranial Interleukin-6 (IL-6) levels have been shown to be elevated during migraine attacks, suggesting that this cytokine may facilitate pain signaling from the meninges. Here we reported that in awake animals, direct application of IL-6 to the dura produced dose-dependent facial and hindpaw allodynia via activation of the ERK signaling pathway. IL-6 application was also able to increase neuronal excitability in a manner consistent with phosphorylation of Nav1.7. These data provide a cellular mechanism by which IL-6 in the meninges causes sensitization of dural afferents therefore contributing to the pathogenesis of migraine.These findings are discussed in relation to how activation and sensitization of primary afferent neurons might initiate migraine pain signaling and how the research included in this dissertation relates to the development of new therapeutic strategies for migraine.

The depression of immune cell function that is typically observed after prolonged exercise is thought to be largely mediated by increased plasma concentrations of stress hormones and cytokines and possibly oxidative stress. The aims of this thesis were to determine the effects of acute and longer term oral antioxidant supplementation on immunoendocrine responses following prolonged exercise. In study 1 (Chapter 3) it was shown that vitamin C ingested acutely before and during prolonged exercise has little or no effect on immunoendocrine responses. Furthermore, the combined ingestion of vitamin C with carbohydrate provides no additional effects compared with carbohydrate alone. However, when vitamin C was supplemented acutely, 2 h prior to, and during prolonged exercise in addition to on the night before (14 h prior) exercise this limited the fall in neutrophil oxidative burst activity (study 2, Chapter 4). This was probably a result of reduced direct oxidative damage to neutrophils with vitamin C supplementation since there were no effects on the cortisol, interleukin-6, leukocytosis or neutrophilia responses. Longer periods of antioxidant supplementation (2 - 4 weeks) may be effective at blunting the cortisol, leukocytosis and neutrophilia responses to prolonged exercise (Chapters 5 and 6) but this had no effect on in vitro measures of neutrophil function. In study 5 (Chapter 7) it was shown that acute pre-exercise dark chocolate (which contains polyphenols) ingestion has some effects on plasma oxidative stress markers and circulating insulin and glucose responses but not the immunoendocrine responses to prolonged exercise.

This thesis presented the study of carbon-based materials for ultra-sensitive molecular sensing. Reduced Graphene Oxide (rGO), a 2-dimensional one-atomic layer thick carbon material, had the advantage of low-cost, aqueous and industrial-scalable production route. Using rGO as the transducer platform could potentially lower the cost of sensors down to a few dollars per chip. However, there were still limitations in rGO that prevented its widespread usage as a biosensor transducer or in electronics: its low electrical conductivity and large electrical deviations. This thesis was structured to understand and solve these problems for transducer application. The thesis could be broken down into 3 parts: The first part of the thesis presented the critical review of the background and limitations of graphene research, followed by the background and importance of biosensor developments for the detection of sweat sodium ions and circulatory Interleukin-6 proteins. The second part of the thesis tested the hypothesis that the rGO limitations could be eliminated to create a highly sensitive biosensor transducer via (A) improving rGO synthesis (B) pristine Carbon Nanotubes-rGO hybrid film and (C) growth of rGO. The mechanism of ultra-large graphene oxide synthesis and graphene oxide growth was also elucidated in this section. The third part of the thesis then presented the fabrication and test of the practical and homogenous carbon-based biosensor using the transducer synthesized earlier. The thesis showed that through proving the hypothesis correct, it enabled the synthesis of an all organic sodium ion sensor with integrated pump and an ultra-sensitive interleukin-6 bio-sensor. Both of these novel sensors were able to detect the respective molecules in their physiological ranges.

A large number of cytokines are expressed in the feet and hands joints of patients with Rheumatoid arthritis. It is necessary to study the new cytokines which may help in prognosis and diagnosis of this autoimmune disease. Omentin1 and Interleukin 20 are the new cytokines and their expressions may have a role in the expression of proinflammatory cytokines; IL-1, IL-6 and TNF, in different cell tissues such as synovial fibroblasts, chondrocytes, peripheral blood mononuclear cells and, sera. It is conceivable that these biomarkers may be used in biological therapies.

Stress can induce prolonged deleterious effects on many characteristics in chickens (Gallus gallus). Particular interest has been paid to early life stress. Social isolation as an early life stressor results in increased plasma corticosterone levels. Moreover, it induces behavioural and physiological changes as well as gene expression modifications in the hypothalamus. In the first part of my study, I aim to inquire into social isolation impacts on the short and long-term. Short and long-term effects were assessed by immune system, behaviour and weight. 82 male chickens were assigned to three groups (stress, control and enrichment). The stress group was exposed to social isolation, the enrichment group was provided with enrichment substrates while the control group was left untreated. According to my knowledge, this is the first study that investigates the effects of social isolation on the interuleikn-6 levels as an indicator of immune system response. My findings suggest that social isolation induces short and long-term effects on immune response as well as on body weight. In the second part of my study, I aim to develop a method investigating effects of early stress on DNA methylation in blood and sperm. For this purpose, two methods GBS (Genotyping by sequencing) and MeDIP (Methylated DNA immuneprecipitation) were f using pooled DNA from all individuals for the first time. Moreover, I developed a protocol for extracting sperm DNA from frozen testis. Combining both methods has many advantages, such as cost effectiveness and the ability to evaluate epigenetic signatures in large number of individuals

A dor aguda pós-operatória tem suscitado grande interesse por seu potencial risco de cronicidade caso não seja adequadamente tratada, podendo piorar a recuperação e a qualidade de vida do paciente. Este estudo comparativo foi realizado de maneira prospectiva, aleatória e encoberta para se avaliar os efeitos sedativos, analgésicos e na resposta inflamatória da administração de metadona ou tramadol. Foram incluídos 28 cães com ruptura de ligamento cruzado e submetidos a osteotomias corretivas, distribuídos em três grupos: TRA - 4 mg/kg de tramadol; MET0,5 - 0,5 mg/kg de metadona e MET0,7 - 0,7 mg/kg de metadona, administrados por via intramuscular na medicação pré-anestésica (MPA). A indução da anestesia foi realizada com propofol e os animais foram intubados e mantidos com isofluorano em oxigênio a 100%. Parâmetros fisiológicos (frequências cardíaca, respiratória e pressão arterial) foram avaliados nos dados momentos: TBL (basal), T1 (uma hora após a MPA), T2 (duas horas após, transcirúrgico), T4 (quatro horas após, pós-cirúrgico), T6 (seis horas após) e T24 (24 horas após). Escores de sedação e dor foram avaliados por escalas em TBL, T1, T4, T6 e T24. Coletas de sangue para mensuração de IL-6 foram realizadas em TBL, T1, T6 e T24. Animais apresentando escores na escala análoga visual maiores que 4, na escala de Glasgow maiores que 5 ou na escala de Colorado maiores que 2, recebiam analgesia complementar com o fármaco do grupo em que foram alocados. Utilizou-se análise de variância para medidas repetidas (ANOVA) com pós teste de Tukey para análise estatística dos parâmetros fisiológicos. Escores de dor e sedação foram comparados entre diferentes momentos por teste de Friedman, seguido de teste de Tukey. Os grupos foram comparados em um mesmo momento, por teste não-paramétrico Kruskal-Wallis, seguido de teste post hoc de Dunn. Valores de p<0,05 expressam diferença significativa. Não houve diferença entre os grupos com relação a idade, peso e sexo, além de tempos de cirurgia e extubação. Os valores de frequência cardíaca, respiratória e pressão arterial mantiveram-se dentro dos parâmetros aceitáveis nas condições avaliadas, havendo redução nos valores em T2 nos grupos MET0,5 e MET 0,7 com relação ao TBL. Para os escores na escala análoga visual, dentro do grupo TRA houve aumento significativo em T4 comparado a TBL, T1 e T24 e entre T1 e T6 (p<0,001). No grupo MET0,5, houve aumento significativo de T1 para T4 (p<0,001). Os grupos TRA e MET0,5 apresentaram médias±DP mais altas (3,4±2,5 e 2,5±2,6, respectivamente) que MET0,7 (1,1±1,5) em T4. Na escala de dor de Glasgow, em MET0,5, houve aumento significativo no momento T4 com relação aos momentos T6 e T24 (p<0,001). No grupo MET0,7, houve aumento significativo no momento T4 para TBL e T24 (p<0,001). Houve maior necessidade de resgate no grupo TRA (quatro animais em T4 e dois em T6), contudo após um incremento na dose do fármaco, obteve-se controle adequado da dor. Não foram observadas diferenças estatísticas significativas quanto ao grau de sedação, escala de Colorado e interleucinas séricas entre os grupos e momentos avaliados. A metadona e o tramadol foram eficazes em promover analgesia pós-operatória quando administrados antes do procedimento cirúrgico e suas doses ajustadas no resgate analgésico. Ambos parecem ter tido efeito sobre a liberação de IL-6, sugerindo modulação da resposta inflamatória aguda / Acute postoperative pain has aroused great interest because of their potential risk of chronification if not treated properly, may worsen the recovery and quality of life of the patient. This clinical trial was conducted in a prospective, randomized, double-blind comparison to evaluate the efficacy of methadone and tramadol as premedication in dogs. 28 animals with ruptured cruciate ligament undergoing corrective osteotomies were divided into three groups: TRA - received 4 mg/kg of tramadol; MET0.5 - received 0.5 mg/kg of methadone and MET0.7 - received 0.7 mg/kg of methadone intramuscularly. Anesthesia induction was performed with propofol and animals intubated for general anesthesia with isoflurane in 100% oxygen. Physiological parameters (heart and respiratory rate and blood pressure) were evaluated at specified times (in hours): TBL (baseline), T1, T2, T4, T6 and T24. Pain and sedation scores were described by use of visual analogue scale (VAS), composite modified Glasgow scale and Colorado scale at TBL, T1, T4, T6 and T24. Blood samples for measurement of IL-6 were performed in moments TBL, T1, T6 and T24. Statistical analysis was performed by ANOVA for repeated measurements. Pain and sedation scores were compared in different times by Friedman\'s test followed by Tukey test. Groups were compared by non-parametric Kruskal-Wallis test followed by post hoc Dunn\'s test. Values with p <0.05 were considered significant. There was no statistically significant difference among groups with respect to age, weight, gender, time of surgery and time for extubation. Heart rate, respiratory rate and blood pressure values were maintained within acceptable values and a reduction was observed in T2 in groups MET0.5 and MET0.7 in relation to TBL. Increases in VAS scores were observed in TRA in T4 compared to TBL, T1 and T24 and between T1 and T6 (p<0.001). In MET0.5 there was a significant increase in T4 when compared to T1 (p<0.001). Groups TRA and MET0.5 showed higher mean±SD values (3.4±2.5 and 2.5±2.6, respectively) than MET0.7 (1.1±1.5) in T4. In Glasgow pains scale, there was significant increase in T4 when compared to T6 and T24 (p<0.001). In MET0.7, T4 showed higher scores than TBL and T24 (p<0.001). TRA showed greater demand of rescue analgesia (four animals in T4 and two in T6), however after a dose adjustment pain was controlled. There were no statistically significant differences in degree of sedation, Colorado acute pain scale and serum interleukin among groups and time points assessed. Both drugs were effective in promoting postoperative analgesia when administered prior to surgical procedure and the doses adjusted according to demand. The drugs appear to have an effect on the release of IL-6, suggesting acute inflammatory response modulation

Anemia em idosos está relacionada ao aumento da morbidade e mortalidade desta população. As causas das anemias em idosos podem ser divididas em três grupos: anemia das doenças crônicas (ADC), anemia por deficiência de nutrientes, na qual se inclui a anemia por deficiência de ferro (ADF) e anemias de causas não-identificadas. A hepcidina constitui uma importante ligação entre defesa primária, inflamação e metabolismo do ferro. A hepcidina é induzida, principalmente, pela interleucina-6 (IL-6), atua como regulador negativo da absorção de ferro e é mediadora da retenção de ferro por monócitos e macrófagos durante inflamação ou infecção. Estudos recentes têm demonstrado o papel da produção desse hormônio por monócitos na homeostase do ferro, num modelo autócrino e parácrino. O presente trabalho teve por objetivo geral correlacionar os níveis de IL-6 produzidos por monócitos em cultura e a expressão de hepcidina em monócitos de indivíduos com ADC, com inflamação sem anemia, ADF e com anemias não-identificadas e, por objetivos específicos, verificar a eficiência de parâmetros hematológicos clássicos em avaliar o status férrico de idosos; comparar os níveis de IL-6 produzidos por células monocíticas em cultura, nos diferentes grupos de estudo, e relacioná-los com os parâmetros utilizados para caracterização das anemias; comparar os níveis de expressão de hepcidina em células monocíticas, nos diferentes grupos de estudo, e relacioná-los com o estado inflamatório e com os parâmetros utilizados para caracterização das anemias. Para isso, os pacientes foram avaliados através de parâmetro bioquímicos (glicemia, creatinina sérica, -glutamil transferase, proteínas totais e albumina, por método colorimétrico e proteína C-reativa, por imunoturbidimetria ultra-sensível) e hematológicos (hemograma completo, utilizando o contador de células Micros 45 ABX®, França, e extensão sangüínea corada por Leishman, ferritina sérica, por método imunoquimioluminescente, receptor de transferrina solúvel, por ensaio imunoenzimático e cálculo do índice sTfR/log ferritina). A determinação dos níveis de IL-6 foi feita por imunoensaio enzimático quantitativo em sobrenadante de cultura de monócitos e a dos níveis de expressão do RNAm da hepcidina em monócitos pela Reação em Cadeia da Polimerase em Tempo Real (RT-PCR). Os níveis séricos de ferritina estavam estatisticamente diminuídos na população com ADF, embora sem atingir os valores preconizados para diagnóstico de deficiência de ferro. Os níveis de receptor de transferrina solúvel (sTfR) e o índice sTfR/log ferritina estavam elevados em pacientes com ADF, porém, o índice não aumentou a sensibilidade da medida do receptor para pacientes idosos. Estes resultados obtidos sugerem que valores de normalidade para níveis de ferritina e índice receptor-ferritina devem ser revistos para a população idosa. Houve aumento da concentração de IL-6 em sobrenadante de cultura de monócitos no grupo Inflamação quando comparado com o grupo Anemia. Os níveis de IL-6 correlacionaram-se positivamente com os níveis da proteína C-reativa e número de leucócitos da população em estudo, porém, não houve correlação com os níveis de RNAm de hepcidina expressos por monócitos. A expressão de RNAm de hepcidina em monócitos mostrou correlação positiva com os níveis séricos de ferritina, porém, não foi diferente entre os grupos de estudo. / Anemia in elderly is associated with increased morbidity and mortality in this population. The causes of anemia in elderly can be divided into three groups: anemia of chronic diseases (ACD), anemia of nutrients deficiency, which include iron deficiency anemia (IDA) and unexplained anemias. Hepcidin is an important link between primary defense, inflammation and iron metabolism. The hepcidin is mainly induced by the Interleukin-6 (IL-6), it acts as a negative regulator of iron absorption and it is mediating of iron retention by monocytes and macrophages during inflammation or infection. Recent studies have been demonstrating the role of this hormone production by monocytes in the iron homeostasis, in autocrine and paracrine fashion. The general objective of this study was to correlate the levels of monocyte-derived IL-6 in culture and the monocyte hepcidin mRNA expression in patients with ACD, with inflammation without anemia, IDA and with unexplained anemias. The specific objectives are to verify the efficiency of classic haematological parameters in evaluating the iron status in elderly; to compare the levels of monocyte-derived IL-6 in culture, in different study groups, and to relate them with the parameters used for anemias characterization; to compare the levels of monocyte hepcidin mRNA expression, in different study groups, and to relate them with the inflammatory state and with the parameters used for anemias characterization. For that, the patients were evaluated by biochemical parameter (blood glucose, serum creatinine, -glutamyl transferase, total proteins and albumin, by colorimetric method and high-sensitivity C-reactive protein, measured by immunoturbidimetric assay) and hematological (complete blood count, using the cells accountant Micros 45 ABX®, and peripheral blood film for Leishmans staining morphology, serum ferritin level by immuno-quimioluminescent assay, soluble transferrin receptor, by Enzyme Linked Immuno Sorbent Assay (ELISA) and sTfR/log ferritin index). The determination of IL-6 levels was performed by quantitative ELISA in monocyte culture supernatants and monocyte hepcidin mRNA levels by Real-Time Polymerase Chain Reaction (RT-PCR). Although serum ferritin levels were statistically decreased in IDA population, it did not reach the values recommended for diagnosis of iron deficiency. The soluble transferrin receptor (sTfR) levels and the sTfR/log ferritin index were significantly higher in IDA group, however, the index did not increase the sensibility of the sTfR measure for elderly. These results suggest that normality values for ferritin levels and sTfR/log ferritin index should be reviewed for elderly population. There was increase of levels of monocyte-derived IL-6 in culture in Inflammation group compared with Anemia group. The IL-6 levels were positively correlated with C-reactive protein levels and leukocyte number of the patients, however, there was not correlation with monocyte hepcidin mRNA levels. The monocyte hepcidin mRNA levels showed positive correlation serum ferritin levels, however, it was not different between the study groups.