Low-dose interleukin 2 antidepressant potentiation in unipolar and bipolar depression: Safety, efficacy, and immunological biomarkers

Abstract

AbstractImmune-inflammatory mechanisms are promising targets for antidepressant pharmacology. Based on reported immune cell abnormalities, we defined an antidepressant potentiation treatment with add-on low-dose interleukin 2 (IL-2), a T-cell growth factor of proven anti-inflammatory efficacy in autoimmune conditions, increasing thymic production of naïve CD4+ T cells, and possibly correcting the partial T cell defect observed in mood disorders. We performed a single-center, randomised, double-blind, placebo-controlled phase II trial evaluating the safety, clinical efficacy and biological responses of low-dose IL-2 in depressed patients with MDD or BD. 36 consecutively recruited inpatients at the Mood Disorder Unit were randomised in a 2:1 ratio to receive either aldesleukin (12 MDD and 12 BD) or placebo (6 MDD and 6 BD). Active treatment significantly potentiated antidepressant response to ongoing SSRI/SNRI treatment in both diagnostic groups, and expanded the population of Treg, Th2, and Naive CD4+/CD8+ immune cell counts. Changes in cell counts were rapidly induced in the first five days of treatment, and predicted the later improvement of depression severity. No serious adverse effect was observed. This is the first RCT evidence supporting the hypothesis that treatment to strengthen the T cell system could be a successful way to correct the immuno-inflammatory abnormalities associated with mood disorders, and potentiate antidepressant response.HighlightsImmune-inflammatory mechanisms are promising targets for antidepressant pharmacology. In a randomized controlled trial low-dose IL-2 significantly improved antidepressant response. IL-2 rapidly expanded the population of Treg, Th2, and Naive CD4+/CD8+ immune cell counts. Strengthening in the T cell system predicted antidepressant response.