The Role of Interleukin-8 (IL-8) in Treatment-Resistant Depression: A Review of Mechanisms, Biomarker Potential, and Therapeutic Implications

TL;DR

This paper reviews how IL-8, a chemokine, may play a role in treatment-resistant depression and could serve as a potential biomarker or therapeutic target.

Contribution

The paper provides a comprehensive review of IL-8's role in treatment-resistant depression, highlighting its potential as a biomarker and therapeutic target.

Findings

IL-8 levels may predict treatment response to antidepressants like ketamine.

Methodological variability and small sample sizes limit current findings on IL-8 in depression.

Future studies are needed to validate IL-8's role in psychiatric precision medicine.

Abstract

Treatment-resistant depression (TRD) remains a major clinical challenge, with a substantial proportion of patients with major depressive disorder (MDD) failing to respond to conventional antidepressant therapies. Increasing evidence suggests that dysregulation of immune signaling contributes to the pathophysiology of TRD. While proinflammatory cytokines such as IL-6 and TNF-α have been extensively studied, less is known about the role of chemokines such as interleukin-8 (IL-8). This review aims to synthesize current knowledge on the biological functions of IL-8, its involvement in neuroimmune mechanisms, and its potential as a biomarker and therapeutic target in treatment-resistant depression. Clinical and preclinical studies evaluating IL-8 levels in MDD and TRD patients were discussed with a focus on treatment response, neuroinflammatory pathways, and predictive modeling. Methodological factors affecting IL-8 measurement and interpretation were critically assessed. Even though clinical studies indicate that IL-8 levels may predict treatment response to antidepressants, including ketamine, findings are inconsistent, partly due to methodological variability, small sample sizes, and confounding factors such as comorbid medical conditions. Therefore, future longitudinal and multimodal studies are warranted to validate its utility in psychiatric precision medicine.

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