Fig 4.

Systemic and local regulation of joint inflammation. Pro-inflammatory cytokines released during joint inflammation lead to an increase in the level of cortisol within the systemic circulation through activation of the hypothalamic–pituitary–adrenal axis (HPA) axis. These cytokines also cause an activation of local glucocorticoid generation through an increase in 11β-hydroxysteroid dehydrogenase 1 (11β–HSD1) activity. ACTH = adrenocorticotropic hormone; IL-1β = interleukin 1β; TNFα = tumour necrosis factor α.