| Author | Brustolim, Daniele | |
| Author | Santos, Ricardo Ribeiro dos | |
| Author | Kast, R. E. | |
| Author | Altschuler, E. L. | |
| Author | Soares, Milena Botelho Pereira | |
| Access date | 2011-07-01T18:17:31Z | |
| Available date | 2011-07-01T18:17:31Z | |
| Document date | 2006 | |
| Citation | BRUSTOLIM, D. et al. A new chapter opens in anti-inflammatory treatments: the antidepressant bupropion lowers production of tumor necrosis factor-alpha and interferon-gamma in mice. International Immunopharmacology, v. 6, n. 6, p. 903-907, 2006. | pt_BR |
| ISSN | 1567-5769 | |
| URI | https://www.arca.fiocruz.br/handle/icict/2741 | |
| Language | eng | pt_BR |
| Rights | open access | en |
| Subject in Portuguese | Bupropiona | pt_BR |
| Subject in Portuguese | Doença de Crohn | pt_BR |
| Subject in Portuguese | Dopamina | pt_BR |
| Subject in Portuguese | Inflamação | pt_BR |
| Subject in Portuguese | Interferon gama | pt_BR |
| Subject in Portuguese | Norepinefrina | pt_BR |
| Subject in Portuguese | Fator de necrose tumoral alfa | pt_BR |
| Title | A new chapter opens in anti-inflammatory treatments: the antidepressant bupropion lowers production of tumor necrosis factor-alpha and interferon-gamma in mice | pt_BR |
| Type | Article | pt_BR |
| DOI | 10.1016/j.intimp.2005.12.007 | |
| Abstract | In a wide range of human diseases of inflammatory nature like Crohn's disease, pathology is mediated in part by proinflammatory
cytokines like tumor necrosis factor-alpha (TNF) or interferon-gamma. We show here that a commonly used generic
antidepressant bupropion, in wide use worldwide to treat depression in humans for a decade now, profoundly lowers levels of TNF,
interferon-gamma, and interleukin-1 beta in vivo, in a mouse lipopolysaccharide (LPS) induced inflammation model. Mice
challenged with an otherwise lethal dose of LPS were protected by bupropion and levels of the anti-inflammatory cytokine
interleukin-10 were increased. Previous data in rodents and humans indicate antidepressant effects of bupropion are mediated by its
weak reuptake inhibition of norepinephrine and dopamine. Concordant with this, TNF suppression by bupropion in our mouse LPS
model was largely abrogated by beta-adrenergic or dopamine D1 receptor antagonists but not by a D2 antagonist. TNF synthesis is
controlled by an inverse relationship with intracellular cyclic adenosine monophosphate (cAMP) and stimulation of either betaadrenoreceptors
or D1 dopaminergic receptors result in increased cAMP but stimulation of D2 receptors lowers cAMP. We
conclude that bupropion may suppress TNF synthesis by mediating increased signaling at beta-adrenoreceptors and D1 receptors,
resulting in increased cAMP that inhibits TNF synthesis. Bupropion is well tolerated also in non-psychiatric populations and has
less risk with long term use than current anti-inflammatory, immunosuppressive or TNF suppressive treatments such as prednisone,
azathioprine, infliximab, or methotrexate. New anti-inflammatory treatments are needed. We believe a new chapter in
antiinflammatory, TNF lowering treatment of disease has been opened. Bupropion's use for this in humans should be explored.
© 2006 Elsevier B.V. All rights reserved. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
| Affilliation | University of Vermont. Department of Psychiatry. Vermont, USA | pt_BR |
| Affilliation | New Jersey School of Medicine and Dentistry. Department of Physical Medicine and Rehabilitation, USA | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
| Subject | Bupropion | pt_BR |
| Subject | Crohn's disease | pt_BR |
| Subject | Dopamine | pt_BR |
| Subject | Inflammation | pt_BR |
| Subject | Interferon-gamma | pt_BR |
| Subject | Norepinephrine | pt_BR |
| Subject | Tumor necrosis factor-alpha | pt_BR |
| DeCS | Bupropiona | pt_BR |
| DeCS | Doença de Crohn | pt_BR |
| DeCS | Dopamina | pt_BR |
| DeCS | Inflamação | pt_BR |
| DeCS | Interferon gama | pt_BR |
| DeCS | Norepinefrina | pt_BR |
| DeCS | Fator de Necrose Tumoral alfa | pt_BR |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
