A novel aspect for depression and cytokine hypothesis: 'NLRP3 inflammasome'

At present, 1/3 of patients diagnosed with major depression do not respond to the current pharmacological treatments acting on monoaminergic neurotransmission has shown that the monoaminergic hypothesis alone, remains inconclusive for highlighting the pathogenesis of depression. It has been shown by several clinical and experimental studies that high serum plasma levels of proinflammatory cytokines such as IL-1 beta, IL-6, TNF-alpha are related with depressive status. Besides, with the antidepressant treatment acting on serotonergic system, there is a decrease in cytokine levels of depressive patients and antidepressant-like effects are observed with the use of immune suppressant drugs acting on cytokines mediated mechanisms. On the other hand, inflammatory cytokines have been proposed to contribute the increase in activation of hypothalamus-pituitary-adrenal (HPA) axis, in parallel with elevated plasma cortisol levels in depressed patients. With the establishment of cytokine hypothesis in depression, the initiating mechanisms of inflammatory processes have become important issues. NLRP3 inflammasome is a multiprotein complex, known to be responsible for initiating the inflammatory mechanisms mediated with IL-1 beta, one of the major proinflammatory cytokine investigated in depression, and also IL-18. It results from the activation of Nod like receptor protein 3 (NLRP3) which is a cytosolic receptor protein especially located in macrophage and microglia. Investigating NLRP3 inflammasome and related pathways in depression could be accepted as an intriguing subject for possibly bringing a new aspect to cytokine hypothesis and further approach for antidepressant therapies.