Zhu_2026_J.Inflamm.Res_19_612518

OBJECTIVE: To compare serum choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) levels between septic and non-septic critically ill patients, and to evaluate their dynamic changes, associations with inflammatory markers, disease severity, and prognosis in sepsis. METHODS: In this prospective observational study, 87 patients with sepsis and 93 non-septic critically ill controls were enrolled. Blood samples were collected from septic patients within 12 hours (T1), 24 hours (T2), 48 hours (T3), and 7 days (T4) after intensive care unit (ICU) admission, while the non-septic group underwent sampling only at T1. Serum levels of ChAT, AChE, and inflammatory cytokines (IL-6, IL-10, TNF-alpha) were measured. A linear mixed model was used to analyze dynamic changes, repeated measures correlation (rmcorr) to assess associations between variables, receiver operating characteristic curves to evaluate discriminative ability, and multivariable logistic regression to identify independent influencing factors. RESULTS: Septic patients had significantly lower ChAT at T1 than non-septic controls (P<0.001), whereas AChE levels did not differ. Both ChAT and AChE were lower in septic shock than in non-shock septic patients (both P<0.05). Linear mixedmodel analysis revealed a significant overall group effect for AChE, with lower levels in nonsurvivors (group effect, P = 0.013); however, no significant intergroup difference was observed at T1 (P = 0.098). ChAT showed moderate discriminative ability for sepsis, with an area under the ROC curve of 0.70, and was identified as an independent factor associated with sepsis in this exploratory cohort (OR = 0.85, 95% CI: 0.76-0.94, P = 0.001). The inverse association between ChAT and sepsis was stronger in patients aged <=65 years (interaction P=0.023). CONCLUSION: This exploratory study demonstrates that serum ChAT levels are significantly decreased in septic patients, correlate with disease severity, and show moderate discriminative ability for sepsis. Linear mixedmodel analysis revealed that AChE levels were overall lower in nonsurvivors than in survivors, although the prognostic value at individual time points was limited. Age modifies the ChAT-sepsis association, which should be considered in clinical evaluation.