Remodelación cardíaca e inflamación / Cardiac remodeling and inflammation

The cardiac remodeling is a progressive response of the heart to acute and chronic insults regardless its etiology. This process is characterized by changes in the size, shape and function and is associated with a worse prognosis in patients with heart failure. The acute myocardial infarction is the most common cause of remodeling. In the first minutes after injury in the ischemic zone there is an important augment in the synthesis and release of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) interleukin-6 (IL-6), interleukin-1-beta (IL-1beta) and transforming growth factor 1-beta (TGF-1beta). This acute releasing of cytokines could regulate the survival or apoptosis of myocytes in infarcted zone and, their negative inotropic effects could represent an adaptative response to delimit the injury and to decrease myocardial energy demand. This significant upregulation of proinflammatory cytokines can extend to noninfarcted zone and triggers a second phase of elevated levels of cytokines that promote interstitial fibrosis and collagen deposition in the contralateral noninfarcted myocardium leading to a dysfunctional ventricle. This article will review the recent reports that support the idea of a cardioprotective role for this early inflammatory response and a deleterious role of the delayed response that mediate the fibrosis that is a typical feature of the remodeling process.

The balance between the production of tumor necrosis factor-alpha and interleukin-10 determines tissue injury and lethality during intestinal ischemia and reperfusion

A major goal in the treatment of acute ischemia of a vascular territory is to restore blood flow to normal values, i.e. to "reperfuse" the ischemic vascular bed. However, reperfusion of ischemic tissues is associated with local and systemic leukocyte activation and trafficking, endothelial barrier dysfunction in postcapillary venules, enhanced production of inflammatory mediators and great lethality. This phenomenon has been referred to as "reperfusion injury" and several studies demonstrated that injury is dependent on neutrophil recruitment. Furthermore, ischemia and reperfusion injury is associated with the coordinated activation of a series of cytokines and adhesion molecules. Among the mediators of the inflammatory cascade released, TNF-alpha appears to play an essential role for the reperfusion-associated injury. On the other hand, the release of IL-10 modulates pro-inflammatory cytokine production and reperfusion-associated tissue injury. IL-1beta, PAF and bradykinin are mediators involved in ischemia and reperfusion injury by regulating the balance between TNF-alpha and IL-10 production. Strategies that enhance IL-10 and/or prevent TNF-alpha concentration may be useful as therapeutic adjuvants in the treatment of the tissue injury that follows ischemia and reperfusion.

Interleukin-1 and nitric oxide increase NADPH oxidase activity in human coronary artery smooth muscle cells

Cytokines, nitric oxide [NO] and reactive oxygen species [ROS] are well known for their pathogenic effects in development of cardiovascular diseases. Interleukin-1 [IL-1] is known to induce NO generation, however it is not well established if IL-1beta or NO regulate production of ROS, such as superoxide anion. Therefore, the main objective of this study was to evaluate the effect of IL-1beta or NO on enzyme activity of NADPH oxidase [NOX], a superoxide-generating system recently documented to participate in a variety of vascular functions. Human coronary artery smooth muscle cells [SMC] obtained from Clonetics were treated with IL-1 beta and NO donor, sodium nitroprusside [SNP], in culture. Nitrites accumulated in supernatants of SMC cultures were measured as an index of NO released following treatment with IL-1beta. NOX enzyme activity was assayed using cytochrome c as the electron acceptor. Treatment with IL-1beta resulted in a 3-fold increase in the production of NO by SMC. Both IL-1beta and SNP enhanced NOX activity, by 67 and 45%, respectively, following 24 h of treatment. This study suggests that NO or NO- generating cytokines might regulate the production of ROS in the cardiovascular system through modulation of superoxide-generating systems such as NOX

The neuroimmune-endocrine axis: pathophysiological implications for the central nervous system cytokines and hypothalamus-pituitary-adrenal hormone dynamics

Cytokines are molecules that were initially discovered in the immune system as mediators of communication between various types of immune cells. However, it soon became evident that cytokines exert profound effects on key functions of the central nervous system, such as food intake, fever, neuroendocrine regulation, long-term potentiation, and behavior. In the 80's and 90's our group and others discovered that the genes encoding various cytokines and their receptors are expressed in vascular, glial, and neuronal structures of the adult brain. Most cytokines act through cell surface receptors that have one transmembrane domain and which transduce a signal through the JAK/STAT pathway. Of particular physiological and pathophysiological relevance is the fact that cytokines are potent regulators of hypothalamic neuropeptidergic systems that maintain neuroendocrine homeostasis and which regulate the body's response to stress. The mechanisms by which cytokine signaling affects the function of stress-related neuroendocrine systems are reviewed in this article.

Factores genéticos del huésped en las enfermedades periodontales / Host genetic factors in periodontal diseases

Hasta tiempos recientes, la periodoncia estuvo orientada a determinar las noxas externas, lo que determinó un oscurecimiento de la participación de otros factores, tales como el genético. El objetivo del presente artículo es brindar al lector una visión de la combinación de la perspectiva molecular de la genética con la de la patogenia de las enfermedades periodontales

Role of cytokines, prostaglandins and nitric oxide in hepatic regeneration

The liver is considered the center of the metabolism. Many of its functions are controlled by a network of mediators. Hepatic regeneration is a highly regulated event also by several substances. Herein is was reviewed the literature about the role of cytokines, prostaglandins and nitric oxide in this event. Prior, it was described the known activities of each substance in the body. Further, it was examined since the production until the action of each one in regenerating livers. We could conclude that some of these mediators present a well-defined action, while others are object of great controversy. Overall, the comprehension of the liver's regeneration is very important in concern to develop new kinds of treatment in hepatology.

Patogênese da nefropatia diabética: o papel das citocinas / Pathogenesis of diabetic nephropathy: citokines role

Os autores abordam a patogênese da nefropatia diabética (ND) em seus aspectos hemodinâmicos-renais e metabólicos, com ênfase na formaçäo da matriz extra celular (MEC). O aumento da pressäo capilar intra-glomerular é um fator patogenético bem estabelecido, mas seu mecanismo de lesäo, embora desconhecido, pode envolver distensäo glomerular, levando a um aumento da produçäo de MEC. Existe entretanto um efeito direto da glicose, observado em glomérulos in vitro, onde altas concentraçöes de glicose estimulam o aumento de síntese da MEC. Este efeito pode ser tanto direto, via ativaçäo da proteina quinase C, como indireto pela formaçäo de produtos de glicosilaçäo nao-enzimática ou pela ativaçao da via dos polióis. O TGF-beta (Transforming Growth Factor Beta) é uma citocina que promove aumento de síntese e a reduçäo da degradaçao da MEC, levando ao acúmulo desta. Aumentos dos níveis de RNAm para TGF-beta no glomérulo de ratos diabéticos já foram documentados nas fases iniciais da ND experimental e a presença de reaçäo imunohistoquímica para TGF-beta já foi detectada em ratos e em pacientes com ND estabelecida. O TGF-beta também regula, in vitro, o aumento de síntese de MEC induzido pela angiotensina II e pelo tromboxane A2. A IGF-1 (Insulin Growth Factor-1) pode ter papel significativo na hipertrofia renal diabética, enquanto que o TNF-alpha (Tumor Necrosis Factor) participa na regulaçäo do aumento da permeabilidade do endotélio glomerular. As demais citocinas (EGF, FGF, IL-1, PDGF e TGF-a) ainda precisam ser melhor estudadas.

Participation of TNF-Ó and IL-1 in the pathogenesis of cyclophosphamide-induced hemorrhagic cystitis

The involvement of cytokines TNF-Ó and IL-1 has been investigated in a model of cyclophosphamide (CYP) - induced hemorrhagic cystitis. Male Swiss mice (25-30 g) received CYP in a single ip dose of 100, 200 or 400 mg/kg and were sacrificed 6, 12, 24, 48 and 72 h later. Cystitis was evaluated by determining the changes in bladder wet weight (BW) and plasma protein extravasation (PPE, measured by the Evans blue leakage technique). CYP treatment induced a marked increase in BW and in PPE, which was significant within 6 h and reached maximal values within 12 h (BW, 118 percent, P<0.05; N = 11; and PPE, 824 percent, P<0.05; N = 11), continuing to be significant until 48 h. Pretreatment of animals with whole anti-TNF-Ó serum (25 or 50 µl diluted in 500 µl 0.9 percent saline, ip, 30 min earlier caused a significant reduction in the CYP-induced BW increase in 6-h and 12-h cystitis (82 percent and 91 percent, respectively, P<0.05; N = 6) and...

A modified assay for measuring thymocyte co-stimulatory activity

The observation that murine thymocytes increase their proliferation to interleukin 1 (IL-1) in the presence of phytohemagglutinin (PHA) when pre-incubated with interleukin 2 (IL-2) allowed the introduction of a modified assay for the measurement of IL-1 or the search of thymocyte-inducing proliferative activities in biological samples. Pre-incubation of thymocytes for 24 hr with 50 u/ml IL-2, followed by washings, elicited their maximal response to IL-1 in the usual lymphocyte activating factor (LAF) assay. This suggests that sequential events lead to thymocyte activation. The responsiveness is three to five fold greater than, and the total time of assay is the same as that of the LAF assay. Interestingly, pre-incubation with IL-2 renders thymocytes more sensitive than responsive to crude monocyte conditioned media. The use of the MTT colorimetric method for the assessment of thymocyte proliferation, and of the lectin jacalin as a co-mitogen are suggested as alternatives to be used in co-stimulatory assays

Metabolismo del hueso periodontal: Parte IV. Control local del metabolismo de hueso / Periodontal bone metabolism: Part IV. Local control of bone metabolism

El presente trabajo es el cuarto de una serie de 5 artículos dedicados al estudio del metabolismo del hueso periodontal. En los tres primeros se hizo una descripción de la biología celular del hueso periodontal, de los fenómenos fisiológicos que se encadenan en el ciclo de remodelado óseo y del control sistémico del metabolismo de hueso. El objetivo del presente trabajo es el de presentar una revisión actualizada sobre las diversas sustancias que intervienen en el control local de la fisiología del hueso periodontal. Aunque varían los criterios de clasificación, se puede decir que cuatro familias de sustancias se encargan del control local del metabolismo de hueso: los factores de crecimiento, las monoquinas, las linfoquinas y los derivados del ácido arachidónico (AA). La compleja interacción de estas sustancias entre sí y con respecto a las hormonas osteotrópicas es un fiel reflejo de que la reabsorción y aposición óseas son fenómenos complejos regulados por un estricto control local

Hematopoese: I. Citocinas envolvidas em sua regulaçäo / Hematopoiesis: I. Cytokines involved in its regulation

O estudo da participaçäo direta de citocinas, tais como os fatores estimuladores do crescimento de colônias, as interleucinas, e outros, no controle das etapas da hematopoese, vem sendo prejudicado pela presença in vitro de células näo-hematopoéticas, capazes de intermediar os efeitos das citocinas sobre os precursores hematopoéticos. Recentemente pôde-se verificar que o antígeno CD34 se expressa na membrana de essencialmente todas as células pluripotenciais, mas näo da maioria das células diferenciadas do sangue ou do estroma da medula óssea, o que veios a permitir experimentos in vitro com populaçöes ricas em células pluripotenciais, purificadas com base na expressäo deste antígeno. Tais experimentos permitiram uma reavaliaçäo dos resultados obtidos previamente com populaçöes menos puras e ampliaram o conhecimento sobre a participaçäo das diferentes citocinas nos processos de diferenciaçäo das distintas linhagens hematopoéticas, tema desta revisäo. O papel de interferons, fatores necrosantes de tumor e fatores de transformaçäo de crescimento ß na regulaçäo negativa da hematopoese säo também analisados

El queratinocito: una celula inmunologica / The keratinocyte: an inmunological cell

El queratinocito es una celula inmunologica que participa activamente en la respuesta inflamatoria e inmunologica. Se efectua una revision de los conocimientos sobre las multiples funciones de esta celula epitelial