A comparative examination of the anti-inflammatory effects of SSRI and SNRI antidepressants on LPS stimulated microglia

作者：Tynan Ross J; Weidenhofer Judith; Hinwood Madeleine; Cairns Murray J; Day Trevor A; Walker Frederick R^*

来源：Brain, Behavior, and Immunity, 2012, 26(3): 469-479.

DOI：10.1016/j.bbi.2011.12.011

• Antidepressant
• SSRI
• SNRI
• TNF-alpha
• Nitric oxide
• LPS
• Anti-inflammatory
• Microglia
• BV-2

Selective serotonin and serotonin norepinephrine reuptake inhibitors (SSRI; SNRI) are the first choice pharmacological treatment options for major depression. It has long been assumed that the primary therapeutic mechanism of action of these drugs involves the modulation of monoaminergic systems. However, contemporary investigations have revealed that depression is linked with inflammation, and that SSRI/SNRIs possess significant anti-inflammatory actions. While these anti-inflammatory properties initially only related to work undertaken on cells of the peripheral immune system, it has recently become apparent that these drugs also exert anti-inflammatory effects on microglia, the principal cells within the CNS that regulate and respond to inflammatory factors. The aim of the current study was to compare SSRI/SNRIs in terms of their anti-inflammatory potency, and to determine the specific mechanisms through which these effects are mediated. Accordingly, the current study evaluated the ability of five different SSRIs (fluoxetine, sertraline, paroxetine, fluvoxamine and citalopram) and one SNRI (venlafaxine) to suppress microglial responses to an inflammatory stimulus. Specifically, we examined their ability to alter tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) production after 4 and 24 h stimulation with lipopolysaccharide. Our results indicated that the SSRIs potently inhibited microglial TNF-alpha and NO production. We then investigated whether these effects might involve either beta-adrenoceptor or cAMP signalling. Using the protein kinase A inhibitor Rp-CAMPs, we found evidence to suggest that cAMP signalling is involved in regulating the anti-inflammatory response. These findings suggest that antidepressants may owe at least some of their therapeutic effectiveness to their anti-inflammatory properties.

• 出版日期2012-3