Study on anti-inflammatory and immunomodulatory effects of fluoxetine in rat models of inflammation

Abstract

The aim of the present study was to evaluate the anti-inflammatory effect of fluoxetine in carrageenan-and lipoplysaccharideinduced models of inflammation by investigating the changes in serum levels of pro-inflammatory cytokine TNF-α and anti-inflammatory cytokines IL-10 and TGF-β after single and repeated administration of the drug. To study the effect of a single and repeated dose fluoxetine on carrageenan-induced paw edema male Wistar rats were divided into five groups (n = 8): control group; positive control group; and three experimental groups treated with 5, 10, and 20 mg/kg bodyweight (bw) fluoxetine, respectively. To study the effect of a single and repeated dose of fluoxetine on serum cytokine levels, the animals were divided in four groups (n = 8): two control groups treated with saline and two experimental groups treated with fluoxetine 20 mg/kg bw. Carrageenan and LPS were injected immediately after fluoxetine or saline injection. Serum cytokine concentrations were tested by enzyme immunoassay. In single administration only the highest dose used inhibited carrageenan-induced inflammation. Edema inhibition was seen with 10 and 20 mg/kg bw fluoxetine after repeated administration. At 24 h a statistically significant effect on inhibition of carrageenan edema was found only in rats treated with 20 mg/kg bw fluoxetine In carrageenan-induced inflammation, fluoxetine significantly increased Il-10 and decreased TNF-α after repeated administration. Surprisingly, in single-dose treated animals an increase in TNF-α values upon fluoxetine administration was observed in this model of inflammation. In LPS-induced inflammation, fluoxetine significantly decreased TNF-α after single and repeated treatment. Fluoxetine has anti-inflammatory and immunomodulatory effect in the carrageenan-induced model of exudative inflammation. In LPS-induced inflammation it showed an immunomodulatory effect manifested with a decrease in pro-inflammatory cytokine TNF-α.

Musk (Moschus moschiferus) Attenuates Changes in Main Olfactory Bulb of Depressed Mice: Behavioral, Biochemical, and Histopathological Evidence

“…Previous research reported that Flu relieved the behavioral changes and improved the structural deteriorations that occurred in the hippocampal regions of mice exposed to CUMS in accordance with our results (CB Filho et al, 2015;Ali et al, 2017;Ayuob et al, 2018). Although some studies have reported that Flu has anti-inflammatory activity (Kostadinov et al, 2015) and antioxidant properties (Caiaffo et al, 2016), in this study, administration of Flu has not been associated with a significant changes in proinflammatory cytokines or antioxidant levels. This might be attributed to the relatively short time of Flu administration.…”

Proteomic investigation of the prefrontal cortex in the rat clomipramine model of depression

“…Of interest, MIF could also regulate a plethora of cytokines as it has been revealed in our pathway analysis ( Figure 5B). It is possible that clomipramine acutely elevated the levels of cortisol or induced anti-inflammatory cytokine secretion (e.g., interleukin-10 in the serum), as described before [77], and our finding on the elevated level of MIF represents a long-term compensatory mechanism against the triggered changes by adulthood.…”

SIRT1 and SIRT2 modulators reduce LPS-induced inflammation in HAPI microglial cells and protect SH-SY5Y neuronal cells in vitro

“…regarding the influence of fluoxetine on TNF-α in different models of inflammation including acting via the immunosuppressant properties of serotonin, inhibition of the transcription factor NF-κB and inhibition of the phosphorylation of p38 MAPK, or potentially acting as a serotonin antagonist on 5-HT2A receptors (Kostadinov et al, 2015). The present study does not provide data to enable the elucidation of the role of serotonin or the other mentioned pathways' participation in our model.…”

“…It is apparent that fluoxetine can have different effects in different experimental models. For example, fluoxetine reduced TNF-α production in LPS-induced inflammation in rats, and also had an inhibitory effect in carrageenan-induced inflammation following multiple doses, but enhanced TNF-α production in the same model if only given as a single dose (Kostadinov et al, 2015). Hence it is apparent that the dose, frequency/duration of administration and model of inflammation will lead to contrasting observations in relation to the effects of fluoxetine on TNF-α.…”

“…Excessive and protracted neuroinflammation can directly result in acute neurological damage or neuronal death and accelerate long-term neurodegeneration (Lyman et al, 2014). Treatment options for neuroinflammation have been investigated, including clinical trials investigating nonsteroidal anti-inflammatory drugs (NSAIDs) and cytokine-inhibitors (Zhang et al, 2012, Kostadinov et al, 2015, Köhler et al, 2016. Even so, their efficacy in neuroinflammation has not been established.…”