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

Background: In depressed patients, alterations in the hypothalamo-pituitaiy-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. Methods: We examined alterations in plasma levels of tumor necrosis factor-alpha (TNF-alpha), levels of its soluble receptors p55 (sTNF-R p55) and p 75 (sTNF-R p 75) as well as changes in the HPA system junction using the combined dexamethasone/corticotropin-releasing hormone (dex/CRH) test on admission and at discharge in 70 depressed inpatients without inflammation. Results: On admission, TNF-alpha levels were inversely associated with the ACTH response to the combined deA-ICRH test. Changes in TNF-alpha, sTNF-R p55, and sTNF-R p75 plasma levels from admission to discharge were positively correlated with the dex/CRH test outcome at discharge. Subgroup analysis revealed that this association was restricted to those patients achieving remission. In this subgroup, TNF-alpha levels at discharge were also positively correlated with dex/CRH test response at discharge. Conclusions. Our results suggest that elevated HPA axis activity in acute depression suppresses TNF-alpha system activity, while after remission, when HPA axis activity has normalized, the TNF-alpha system seems to gain influence on the HPA system.