Abstract | BACKGROUND:
Antidepressants are heavily prescribed drugs and have been shown to affect inflammatory signals. We examined whether these have anti-inflammatory properties in animal models of septic shock and allergic asthma. We also analysed whether antidepressants act directly on peripheral cell types that participate in the inflammatory response in these diseases. METHODS: RESULTS: In the septic shock model, all three drugs given preventively markedly decreased circulating levels of TNF-alpha and mortality (50% mortality in fluoxetine treated group, 30% in desipramine and prednisolone treated groups versus 90% in controls). In the curative trial, antidepressants had no statistically significant effect, while prednisolone still decreased mortality (60% mortality versus 95% in controls). In ovalbumin-sensitized rats, the three drugs decreased lung inflammation, albeit to different degrees. Prednisolone and fluoxetine reduced the number of macrophages, lymphocytes, neutrophils and eosinophils, while desipramine diminished only the number of macrophages and lymphocytes. However, antidepressants as opposed to prednisolone did not attenuate bronchial hyperreactivity. In vitro, desipramine and fluoxetine dose-dependently inhibited the release of TNF-alpha from LPS-treated monocytes. In lung epithelial cells, these compounds decreased TNF-alpha-induced RANTES expression as well as the activity of nuclear factor-kappaB and activator protein-1. CONCLUSION:
Desipramine and fluoxetine reduce the inflammatory reaction in two animal models of human diseases. These antidepressants act directly on relevant peripheral cell types to decrease expression of inflammatory mediators probably by affecting their gene transcription. Clinical implications of these observations are discussed.
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Authors | Caroline Roumestan, Alain Michel, Florence Bichon, Karine Portet, Maëlle Detoc, Corinne Henriquet, Dany Jaffuel, Marc Mathieu |
Journal | Respiratory research
(Respir Res)
Vol. 8
Pg. 35
(May 03 2007)
ISSN: 1465-993X [Electronic] England |
PMID | 17477857
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Anti-Inflammatory Agents
- Antidepressive Agents
- Cytokines
- Fluoxetine
- Prednisolone
- Desipramine
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Topics |
- Animals
- Anti-Inflammatory Agents
(therapeutic use)
- Antidepressive Agents
(therapeutic use)
- Asthma
(complications, metabolism)
- Cells, Cultured
- Cytokines
(drug effects, metabolism)
- Desipramine
(therapeutic use)
- Disease Models, Animal
- Fluoxetine
(therapeutic use)
- Humans
- Inflammation
(drug therapy, etiology)
- Mice
- Mice, Inbred BALB C
- Monocytes
(drug effects)
- Prednisolone
(therapeutic use)
- Rats
- Respiratory Mucosa
(drug effects)
- Shock, Septic
(complications, metabolism)
- Treatment Outcome
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