Different activation patterns of proinflammatory cytokines in melancholic and non-melancholic major depression are associated with HPA axis activity

Abstract

Background: Recent studies showed an activation of the cytokine system and the HPA axis in major depression, although with inconsistent results. While the non-melancholic subtype displayed a proinflammatory cytokine pattern, the melancholic subtype showed signs of impaired cytokine production. In order to understand the potential pathogenic significance of these systems further, the interplay between the cytokine system and the HPA axis in depressive subtypes as well as potential changes of these systems during the course of disease were investigated.

Methods: N=37 initially unmedicated patients with acute major depression were sub-classified (melancholic vs. non-melancholic) and compared with N=37 matched healthy controls. Upon admission and after complete clinical remission, basal plasma ACTH and serum cortisol levels as well as cytokine productions (IL-1beta, IL-1 receptor antagonist (IL-1RA)) upon mitogen stimulation (PHA) were measured in a whole blood assay.

Results: ACTH and cortisol concentrations were significantly elevated on admission in the melancholic but not the non-melancholic subgroup. Non-melancholic patients produced significantly more IL-1beta and IL-1RA upon admission than controls or melancholic patients. The IL-1 RA/IL-1beta ratio was significantly lower in the non-melancholic compared to the melancholic subgroup and increased significantly upon remission.

Limitations: Patient treatment was not standardized. No Dex/CRH test was performed.

Conclusions: Melancholic patients demonstrated an activation of the HPA axis in acute stage with partial normalization upon remission but no signs of inflammation. Non-melancholic patients showed signs of inflammation in acute depression with normalization upon remission while the function of the HPA axis was normal.