# Interleukins in Major Depressive Disorder: Lessons From Autoimmune Diseases and Pathways to Clinical Translation

## TL;DR

This paper explores how immune dysregulation, especially involving interleukins, contributes to depression and how insights from autoimmune diseases can guide new treatments.

## Contribution

The paper identifies shared and unique inflammatory mechanisms between MDD and autoimmune diseases, proposing a precision immune-psychiatry approach for treatment.

## Key findings

- MDD patients show elevated pro-inflammatory interleukins like IL-6, IL-1β, and IL-18.
- Inflammatory mediators and signaling pathways are shared between MDD and autoimmune diseases.
- Biomarkers like IL-6 can identify an inflammatory subtype of depression for targeted treatment.

## Abstract

Major Depressive Disorder (MDD) is a leading cause of disability, and limitations of the monoamine hypothesis have driven the exploration of complementary models, including the inflammatory hypothesis. This hypothesis suggests that in a subset of patients, immune dysregulation, especially involving interleukins (ILs), contributes to depression. This review compares IL dysregulation in MDD and autoimmune diseases to identify common and unique inflammatory mechanisms for treatment.

Some MDD patients exhibit chronic, low‐grade inflammation both systemically (in blood) and centrally (in CSF and brain). They show elevated pro‐inflammatory IL‐6, IL‐1β, and IL‐18, with insufficient anti‐inflammatory IL‐10. This immune dysregulation affects key neurobiological processes (monoamine metabolism, HPA axis, neurogenesis), linking inflammation to depressive symptoms. MDD and autoimmune diseases share inflammatory mediators and signaling pathways, supporting these as therapeutic targets; however, MDD's inflammation is low‐grade and innate driven, whereas autoimmune diseases have high‐grade, adaptive immune responses to specific antigens. Successful anti‐IL therapies in autoimmune conditions provide a roadmap for treating inflammation‐driven depression. Translating these findings to practice requires a precision immune‐psychiatry approach. Biomarkers like C‐reactive protein and IL‐6 can identify an inflammatory depression subtype, and patients may benefit from targeted immunomodulatory strategies, repurposed biologics, novel small molecules, or lifestyle interventions particularly if standard antidepressants fail.

Major Depressive Disorder (MDD) is a leading cause of disability, and limitations of the monoamine hypothesis have spurred interest in an inflammatory model of depression. Immune dysregulation, especially involving interleukins (ILs), contributes to depression. This affects key neurobiological processes, linking inflammation to depressive symptoms. Depressive disorder and autoimmune diseases share inflammatory mediators and signaling pathways, supporting anti‐IL therapies as therapeutic targets.