Pharmaceuticals (Basel, Switzerland)
June 10, 2025
Layla Bleibel, Paulina Sokołowska, Gabriela Henrykowska et al.
18 citations
Antidepressants like SSRIs, SNRIs, esketamine, and ketamine reduce inflammation in people with depression by lowering pro-inflammatory cytokines or boosting anti-inflammatory cytokines in the blood and brain regions such as the hippocampus and prefrontal cortex. These effects occur through multiple pathways, including NF-κB, the NLRP3 inflammasome, the glutamatergic system, the gut-brain axis, the hypothalamic-pituitary axis, impaired neuroplasticity, and the kynurenine pathway. The findings suggest that anti-inflammatory actions contribute to the therapeutic benefits of these treatments, supporting the link between depression and inflammation.
Cells
June 3, 2025
Marta Jóźwiak-Bębenista, Anna Wiktorowska-Owczarek, Małgorzata Siatkowska et al.
4 citations
Ketamine and its metabolites—including R-ketamine, S-ketamine, and the hydroxynorketamines (2S,6S-HNK and 2R,6R-HNK)—directly reduce markers of endoplasmic reticulum (ER) stress and inflammation in human microglial cells. In cells treated with tunicamycin to induce ER stress, all compounds lowered expression and protein levels of CHOP and GRP78, two key components of the unfolded protein response (UPR). In microglia stimulated with lipopolysaccharide (LPS), the compounds decreased levels of the inflammatory cytokine IL-6 and, to a lesser extent, IL-8. These findings point to a glia-targeted mechanism for modulating ER stress and neuroinflammation, supporting further in vivo research to develop antidepressants with fewer psychoactive side effects than current treatments.
Farmacja Polska
February 3, 2024
Marta Jóźwiak-Bębenista, Paulina Sokołowska, Edward Kowalczyk et al.
In some patients with depression—especially those who do not respond to standard antidepressants or who have suicidal thoughts—inflammation and cytokines contribute to treatment failure. Ketamine, particularly S-ketamine, offers a fast-acting antidepressant option for treatment-resistant depression (TRD). Its antidepressant mechanism is complex and not fully understood, but mainly involves modulating the glutamatergic system, which produces rapid effects and supports neuroplasticity. Recent research highlights ketamine's anti-inflammatory properties and its influence on tryptophan metabolism. This narrative review, based on literature from November 2006 to November 2023, summarizes current knowledge that preclinical and clinical studies show ketamine has anti-inflammatory effects, directly or indirectly activating neuroprotective branches of the kynurenine pathway, at least in some TRD patients.