Work

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

Year: 2026

Type: article

Abstract: BACKGROUND: 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. RESULTS AND CONCLUSION: 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.

Source: CNS Neuroscience & Therapeutics

DOI: 10.1002/cns.70791

Authors: Adnan Akif, Mohammad Fahim Kadir, Md. Rabiul Islam

Institutions: University of Nevada, Reno, Campbell University, BRAC University

Language: English

Topic: Tryptophan and brain disorders

Subfield: Biological Psychiatry

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,140