Successful Antidepressant Therapy Restores the Disturbed Interplay Between TNF-α System and HPA Axis

Background 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. Methods We examined alterations in plasma levels of tumor necrosis factor-α (TNF-α), levels of its soluble receptors p55 (sTNF-R p55) and p75 (sTNF-R p75) as well as changes in the HPA system function 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-α levels were inversely associated with the ACTH response to the combined dex/CRH test. Changes in TNF-α, 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-α 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-α system activity, while after remission, when HPA axis activity has normalized, the TNF-α system seems to gain influence on the HPA system.