Successful antidepressant therapy restores the disturbed interplay between TNF-alpha system and HPA axis

Aims: In depressed patients, alterations in the hypothalamo-pituitary-adrenocortical (HPA) system are the most consistent neurobiological finding. HPA axis activity and cytokines are intrinsically intertwined: inflammatory cytokines stimulate adrenocorticotropic hormone (ACTH) and cortisol secretion, while, in turn, glucocorticoids suppress the synthesis of proinflammatory cytokines. We investigated the association between changes in HPA axis function and cytokine activity during antidepressant treatment in depressed patients. Methods: We examined alterations in plasma tumor necrosis factor-alpha (TNF-a) and its soluble receptor p55 (sTNF-R p55) and p75 (sTNF-R p75) levels as well as changes in HPA system function using the combined dexamethasone / corticotropin-releasing hormone (dex/CRH) test on admission and at discharge in 70 depressed inpatients. Results: On admission, TNF-a levels in depressed inpatients were inversely associated with the neuroendocrine response to the combined dex/CRH test. Changes in TNF-a, sTNF-R p55, and sTNF-R p75 plasma levels from admission to discharge were correlated with the dex/CRH test outcome at discharge. TNF-a tevels at discharge were also positively correlated with neuroendocrine response to the dex/CRH test at discharge. Conclusions: Elevated HPA axis activity in acute depression suppresses TNF-a activity, while at discharge, when HPA axis activity has normalized, the TNF-a system has regained its influence on the HPA system.