Summary of the immune cytokine function in the HPA and its contribution in T2DM and depression
| Cytokine | Target on the HPA axis | Effect on the HPA axis | Contribution in T2DM and depression |
| Interleukin-1β (IL-1β) | Adrenal gland | Influence the release of GC. | Destruction and loss-of-function insulin-producing β cells of the pancreas. Critical mediator of the adaptive stress response where overproduction dysregulates, causing maladaptive sickness response. |
| Interleukin-6 (IL-6) | IL-6 receptors in the hypothalamus | Regulate CRH production and stimulate corticotrophs and ACTH release in CRH deficiency. | Involved in brain signaling, resulting in maladaptive sickness response causes depressive symptoms. Induce insulin resistance. |
| IL-6 receptors of the adrenal gland | Promote glucocorticoid secretion. | ||
| Tumor necrosis factor-alpha (TNF-α) | Mainly the hypothalamus | Depending on CRH, it affects ACTH secretion. | Induce insulin resistance. |
ACTH, adrenocorticotropic hormone; CRH, corticotrophin-releasing hormone; GC, glucocorticoid; HPA, hypothalamic-pituitary-adrenal; T2DM, type 2 diabetes mellitus.