Related Experiment Video
Updated: Aug 5, 2026
Systems Analysis of the Neuroinflammatory and Hemodynamic Response to Traumatic Brain Injury
Published on: May 27, 2022
Mendelian Randomization Analysis of the IL-1 Cytokine Family Proteins Identifies IL1RL1 as a Potential Causal
Youngjune Bhak1, Adel Helmy2, Edward J Needham2
1Department of Medicine, University of Cambridge, Cambridge, UK.
Background:
Traumatic brain injury (TBI) is a leading preventable cause of death and disability worldwide. Inflammatory mechanisms contribute to secondary brain injury, and the interleukin-1 (IL-1) cytokine family has emerged as a potential contributor. However, whether circulating IL-1-family cytokines causally influence TBI outcomes remains unknown.
Methods:
We performed a two-sample Mendelian randomization (MR) analysis to evaluate the causal effects of circulating IL-1-family protein levels on TBI outcomes, using inverse-variance weighting (IVW) as the primary analytic method and publicly available genome-wide association study summary statistics.
Results:
Higher genetically predicted circulating IL1RL1 (soluble ST2) levels were associated with an increased risk of unfavorable TBI outcomes (IVW β = 0.22, standard error [SE] = 0.084, P = 0.010), although we were underpowered to test the reverse direction. Sensitivity analyses demonstrated consistent effect estimates with no evidence of horizontal pleiotropy.
Conclusions:
These findings provide genetic evidence that elevated circulating IL1RL1 levels are causally linked to worse TBI outcomes. This suggests the IL-33/IL1RL1 axis as a mechanistically relevant, and potentially modifiable, therapeutic target for improving recovery after TBI.
