L-arginine abolishes the hypothalamic serotonergic activation induced by central interleukin-1 beta administration to normal rats

IL-1 beta-induced anorexia may depend on interactions of the cytokine with neuropeptides and neurotransmitters of the central nervous system control of energy balance and serotonin is likely to be one catabolic mediator targeted by IL-1 beta. in the complex interplay involved in feeding modulation, nitric oxide has been ascribed a stimulatory action, which could be of significance in counteracting IL-1 beta effects.The present study aims to explore the participation of the nitric oxide and the serotonin systems on the central mechanisms induced by IL-1 beta and the relevance of their putative interactions to IL-1 beta hypophagia in normal rats. Serotonin levels were determined in microdialysates of the ventromedial hypothalamus after a single intracerebroventricular injection of 10 ng of IL-1 beta, with or without the pre-injection of 20 mu g of the nitric oxide precursor L-arginine. IL-1 beta significantly stimulated hypothalamic serotonin extracellular levels, with a peak variation of 130 +/-37% above baseline. IL-1 beta also reduced the 4-h and the 24-h food intakes (by 23% and 58%, respectively). the IL-1 beta-induced serotonergic activation was abolished by the pre-injection of L-arginine while the hypophagic effect was unaffected.The data showed that one central effect of IL-1 beta is serotonergic stimulation in the ventromedial hypothalamus, an action inhibited by nitric oxide activity. It is suggested that, although serotonin participates in IL-1 beta anorexia, other mechanisms recruited by IL-1 beta in normal rats are able to override the absence of the serotonergic hypophagic influence.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Physiol, BR-04023060 São Paulo, BrazilUniversidade Federal de São Paulo, Div Appl Stat, BR-04023060 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol, BR-04023060 São Paulo, BrazilUniversidade Federal de São Paulo, Div Appl Stat, BR-04023060 São Paulo, BrazilWeb of Scienc

Influência dos hormônios adrenocorticais sobre a síntese de fibrinogênio e de haptoglobina em ratos

BV UNIFESP: Teses e dissertaçõe

Participação da alfa2 - macroglobulina, uma proteína de fase aguda, no fenômeno da contra-irritação

BV UNIFESP: Teses e dissertaçõe

A New Strategy for the Identification of Novel Molecules with Targeted Proresolution of Inflammation Properties

As our understanding of inflammatory resolution increases, drugs that trigger proresolution pathways may become significant in treating chronic inflammatory diseases. However, anti-inflammatory drugs are traditionally tested during the first hours of onset (i.e., to dampen leukocyte and edema formation), and their ability to trigger proresolution processes has never been investigated. Moreover, there is no model available to screen for putative proresolving agents. in this study, we present a new strategy to identify therapeutics for their ability to switch inflammation off and restore homeostasis. Injecting 1.0 mg of zymosan i.p. causes transient inflammation characterized by polymorphonuclear neutrophil clearance and dominated by recently described resolution-phase macrophages along with an innate-type lymphocyte repopulation, the latter being a marker of tissue homeostasis. in contrast, 10 mg of zymosan elicits an aggressive response characterized by classically activated macrophages leading to systemic inflammation and impaired lymphocyte repopulation. Although this latter model eventually resolves, it nonetheless represents inflammation in the clinically relevant setting of polymorphonuclear neutrophil/classically activated macrophage dominance driving a cytokine storm. Treating such a reaction therapeutically with proresolution drugs provides quantifiable indices of resolution-polymorphonuclear neutrophil/macrophage clearance, macrophage phenotype switching (classically activated to resolution phase), and repopulation with resolution-phase lymphocytes-cardinal signs of inflammatory resolution and homeostasis in the peritoneum. As an illustration, mice bearing peritonitis induced by 10 mg of zymosan- were given ibuprofen, resolvin El, a prostaglandin D(2) receptor 1 agonist, dexamethasone, rolipram, or azithromycin, and their ability to trigger resolution and homeostasis in this new inflammatory setting was investigated. We present the first model for testing drugs with targeted proresolution properties using quantifiable parameters of inflammatory resolution and homeostasis. the Journal of Immunology, 2010, 184: 1516-1525.Wellcome TrustCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Medical Research Council/Glaxo SmithKline Pilot Industry AwardUCL, Rayne Inst, Div Med, Ctr Clin Pharmacol & Therapeut, London WC1E 6JJ, EnglandGlaxoSmithKline Inc, Resp CEDD, Stevenage, Herts, EnglandUniversidade Federal de São Paulo, Dept Physiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol, São Paulo, BrazilWeb of Scienc

Protective effect of soybean oil- or fish oil-rich diets on allergic airway inflammation

Background: The increased prevalence of asthma and allergic diseases in westernized societies has been associated with increased intake of diets rich in n-6 fatty acids (FAs) and poor in n-3 FAs. This study aimed to analyze the prophylactic effects of treatment with a soybean oil-rich diet (rich in n-6) or fish oil (rich in n-3) in an allergic airway inflammation model on lung inflammation score, leukocyte migration, T-helper cell (Th)-2 (interleukin [IL]-4, IL-5) and Th1 (interferon [IFN]-gamma, tumor necrosis factor-alpha) cytokines, lipoxin A4, nitric oxide, bradykinin, and corticosterone levels in bronchoalveolar lavage (BAL) or lungs. Methods: Male Wistar rats fed with soybean oil-or fish oil-rich diet or standard rat chow were sensitized twice with ovalbumin-alumen and challenged twice with ovalbumin aerosol. The BAL and lungs were examined 24 hours later. Results: Both diets, rich in n-6 or n-3 FAs, impaired the allergic lung inflammation and reduced leukocyte migration, eosinophil and neutrophil percentages, and IL-4/IL-5/bradykinin levels in BAL and/or lungs, as well as increased the nitric oxide levels in BAL. The soybean oil-rich diet additionally increased the levels of lipoxin A4 and corticosterone in the lungs. Conclusion: Data presented demonstrated that the n-6 FA-rich diet had protective effect upon allergic airway inflammation and was as anti-inflammatory as the n-3 FA-rich diet, although through different mechanisms, suggesting that both diets could be considered as complementary therapy or a prophylactic alternative for allergic airway inflammation.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Departamento de Fisiologia, Universidade Federal de São Paulo, São Paulo, BrazilDepartamento de Medicina, Universidade Federal de São Paulo, São Paulo, BrazilDepartamento de Ciências Biológicas, Universidade Federal de São Paulo, Diadema, São Paulo, BrazilDepartamento de Fisiologia, Universidade Federal de São Paulo, São Paulo, BrazilDepartamento de Medicina, Universidade Federal de São Paulo, São Paulo, BrazilDepartamento de Ciências Biológicas, Universidade Federal de São Paulo, Diadema, São Paulo, BrazilFAPESP: 2006/57075-9CNPq: 302213/2010-4Web of Scienc