IL-18 binding protein associates with maintenance of strength after surgery but is negatively associated with muscle strength and physical performance in men with age-related sarcopenia, consistent with known effects of IL-18BP ligands on mitochondrial function.
Key Findings
Results
Surgery significantly altered circulating concentrations of a large number of plasma proteins within 24 hours.
Surgery increased circulating concentrations of 295 proteins and decreased 301 proteins.
Protein levels were quantified by SOMAscan before and 24 hours after surgery.
Patients were experiencing acute sarcopenia following surgery in a well-characterised cohort.
Results
Higher day 1 post-surgery IL-18BP levels were associated with maintenance of handgrip strength over 7 days following surgery.
Analysis of day 1 protein levels from SOMAscan identified IL-18BP as associated with maintenance of strength.
Change in handgrip strength was compared over 7 days in surgery patients.
Baseline SOMAscan data from surgery patients also showed inverse associations of IL-18BP with strength.
Results
IL-18BP was negatively associated with grip strength in men with age-related sarcopenia at baseline and at 12 months.
129 individuals (68 women) with age-related sarcopenia were recruited to the LACE trial.
At baseline, IL-18BP negatively associated with grip strength in men (r = -0.314, p = 0.014).
At 12 months, the association remained significant (r = -0.446, p = 0.001).
This negative association was not observed in women.
Results
IL-18BP was negatively associated with quadriceps maximal voluntary contraction (QMVC) and 6-minute walk distance (6MWD) in the LACE cohort.
QMVC and 6MWD showed similar negative associations with IL-18BP as grip strength.
These associations were observed in the LACE cohort of individuals with age-related sarcopenia.
The direction of association was consistent with reduced physical performance at higher IL-18BP levels.
Results
IL-18BP was positively associated with SARC-F score in men but not women.
In the LACE cohort, IL-18BP was associated with SARC-F in men (r = 0.389, p = 0.003).
No significant association was found between IL-18BP and SARC-F in women.
SARC-F is a validated screening tool for sarcopenia severity.
Results
Circulating IL-18BP levels in surgery patients were negatively correlated with expression of mitochondrial genes in muscle transcriptome data.
Comparison of circulating IL-18BP with the muscle transcriptome in surgery patients showed negative enrichment for mitochondrial genes.
This finding is described as consistent with known effects of IL-18BP ligands on the maintenance of mitochondrial function.
The analysis linked the systemic protein biomarker to tissue-level gene expression changes.
Results
Free IL-18 levels were proportional to 6-minute walk distance in participants.
Analysis of the ligands showed that free IL-18 was proportional to 6MWD.
IL-18 is a ligand of IL-18BP, and the relationship between free IL-18 and physical performance was in the opposite direction to that of IL-18BP.
IL-37, another ligand of IL-18BP, was also quantified by ELISA alongside IL-18 and IL-18BP.
Methods
IL-18BP, IL-18, and IL-37 were quantified using ELISA in both surgery patients and the LACE sarcopenia cohort for validation of proteomic findings.
Initial discovery used SOMAscan proteomic platform; follow-up used ELISA for IL-18BP, IL-18, and IL-37.
The LACE trial enrolled 129 individuals (68 women) with age-related sarcopenia.
Outcome measures included grip strength, QMVC, 6MWD, and SARC-F score.
Paul R, Rossios C, Hinken A, Neil D, Russell A, Witham M, et al.. (2026). IL-18 Binding Protein, a biomarker of strength maintenance after surgery but reduced physical performance in age-related sarcopenia.. PloS one. https://doi.org/10.1371/journal.pone.0340493