Figure 2: The possible change process of inflammatory cytokines in the chronic stress. (i) The chronic stressor disturbs the cytokines homeostasis through activating HPA axis, SAM axis, and vagus fiber, and they, respectively, promote the secretions of GCs, CAs, and Ach to suppress the proinflammatory cytokines secretion while promoting the anti-inflammatory cytokines secretion. (ii) Sustained stressor exposure changes to upregulate the proinflammatory cytokines and downregulate the anti-inflammatory cytokines through the following four pathways: (a) HPA “fatigue”; (b) glucocorticoid-resistance; (c) the inflammation-related transcription pathways (NF-κB, AP-1, JAK-STAT, MAPKs) activation; and (d) organism negative feedback. (iii) The lasting chronic stress further increases the proinflammatory cytokines, which induces inflammatory response and may ultimately cause various diseases.