Systemic immune-metabolic interactions in patients with amyotrophic lateral sclerosis: correlations of plasma...

Amyotrophic lateral sclerosis (ALS) is a clinically heterogeneous disease influenced by multiple biological processes. Altered energy metabolism, particularly hypermetabolism, is observed in some people living with ALS (plwALS) and is associated with faster progression. The mechanisms underlying this metabolic phenotype remain unclear. Inflammation has been proposed as a contributing factor. We examined whether plasma cytokines, as markers of systemic inflammation, are associated with energy expenditure in plwALS.

Plasma samples from 77 plwALS and 90 non-neurodegenerative controls were analyzed using a multiplex immunoassay quantifying 14 cytokines. Cytokine concentrations were compared between groups and examined in relation to body composition, resting energy expenditure, and functional capacity as inferred by the ALSFRS-R.

Interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) concentrations were higher in plwALS than in controls prior to correction for multiple comparisons (p = 0.006; p.adj = 0.083, and p = 0.035; p.adj = 0.237, respectively). Hypermetabolism was more prevalent in the ALS cohort (36% compared to 11.5%, p < 0.001); however, cytokine concentrations were not significantly different across metabolic subgroups and showed no statistically significant association with metabolic index, energy expenditure, or functional measures.

Findings confirm modest elevations in plasma levels of IL-6 and MCP-1 in ALS but provide no evidence that circulating cytokines correlate with hypermetabolism. Further studies integrating longitudinal and tissue-specific analyses are needed to clarify immune-metabolic mechanisms contributing to disease heterogeneity in ALS.