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Updated: Jun 8, 2026
Animal Models of Depression - Chronic Despair Model (CDM)
Published on: September 23, 2021
Circulating IL-17 a as a downstream inflammatory indicator of depression: Insights from mendelian randomization and
Zhenchen Lu1, Qiaoyu Yang1, Shansong Hu1
1School of Pharmacy, Department of Anesthesiology, the Third Affiliated Hospital of Anhui Medical University, Anhui Medical University, Hefei, 230032, China.
Background:
Previous studies have established a strong link between central nervous system inflammation and depression development. However, the role and function of circulating cytokines in depression remain a topic of debate.
Methods:
Bidirectional MR analyses used GWAS data from the GWAS Catalog, UK Biobank, and IEU database, including two depression cohorts and 41 circulating cytokines. Animal experiments explored the association between IL-17 A, IL-1β, and depression by assessing cytokine expression in control and CUMS rats, with or without IL-17 A/IL-1β inhibitors.
Results:
A potential directional association was found between depression and increased circulating IL-17 A (OR: 7.896, 95%CI: 1.962-31.782, P = 0.004, FDR = 0.019), with consistent findings in an independent cohort (OR: 1.732, 95%CI: 1.012-2.963, P = 0.045, FDR = 0.049). Circulating IL-1β was suggested as a risk factor for depression in both cohorts (OR: 1.036, 95%CI: 1.0002-1.0727, P = 0.049, FDR = 0.049; OR = 1.015, 95%CI: 1.002-1.029, P = 0.028, FDR = 0.046). Another MR study suggested IL-17 A exacerbated IL-1β dysregulation in depression (OR: 1.142, 95%CI: 1.034-1.261, P = 0.009, FDR = 0.031; OR: 1.224, 95%CI: 1.093-1.371, P < 0.001, FDR < 0.001). Animal experiments showed dynamic elevations of IL-17 A and IL-1β under CUMS. IL-1β inhibition alleviated depressive-like symptoms, whereas IL-17 A inhibition had little effect.
Conclusion:
Our findings suggest that circulating IL-17 A may serve as a potential downstream inflammatory indicator, but not a causative factor for depression. A mutually reinforcing relationship may exist between elevated IL-1β and IL-17 A and depression.
