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Abstract

The immune system and the central nervous system (CNS) form a bi-directional communication network through cytokines which act as signaling molecules of the immune system as well as producing neuroendocrine, neuroimmune, and behavioral changes in response to a variety of stress stimuli. It has been known that activation of the central innate immune system or exposure to stress can disrupt balance of anti-/proinflammatory cytokines. However the mechanism by which these cytokines regulate the hypothalamic-pituitary-adrenal (HPA) axis is still unclear. To understand the role of cytokines on stress-induced neuroinflammation, we investigated the role of pro- and anti-inflammatory cytokines in the modulation of depressive-like behaviors, the hormonal and neurotransmitter systems in rats. Single exposure of stress resulted in an increase of corticotrophinreleasing factor expression in the paraventricular nucleus of the hypothalamus, adrenocorticotropin hormone and the final hormone of HPA-axis, corticosterone levels in the serum. Peripheral and central productions of pro-inflammatory cytokines, IL-1�² and IL 6 were significantly increased during stress, whereas anti-inflammatory cytokine, IL-4 was reduced after stress stimulation. Based on these animal models, we have screened and evaluated anti-stress and anti-depressant effect of several herbal formula such as soyo-san, a traditional medicinal formula, a mixture of 9 crude drugs including Paeoliae Radix Alba, Atractylodis macrocephalae phizoma, Angelicae gigantis radix, Poria, Liriopis tuber, Bupleuri radix, Menthae herba, Glycyrrhizae radix, Zingiberi rhizoma recens which have been clinically used for treating mild depressive disorders. Soyo-san inhibited stressinduced inflammatory responses, IL-1�² production in the brain as well as effectively reduced behavioral and patho-physiological depression-like responses. These data suggest that stress may potentate inflammation through interaction of cytokines with activation of the HPA axis and stress-related disorders may be influenced by imbalance of pro and anti-inflammatory cytokines. In addition, the immunerestorative compounds such as soyo-san may be useful as powerful therapeutic candidate for treatment of stress-related diseases such as depression.

Biography

Email: ishim@khu.ac.kr