ORIGINAL RESEARCH article
Front. Med.
Sec. Intensive Care Medicine and Anesthesiology
The Role of Cytokines in Acute Gastrointestinal Injury: A Prospective Pilot Study
Provisionally accepted
- 1Intensive care medicine, First Affiliated Hospital of Jilin University, Changchun, China
- 2Jinling Hospital, Medical School of Nanjing University,, nanjing, China
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Objective: To investigate the association between cytokines and the severity of acute gastrointestinal injury (AGI) in critically ill patients on day 3 after ICU admission. Methods: This was a single-center, prospective observational cohort study. We collected blood samples for five consecutive days and measured IL-6, IL-10, TNF-α, I-FABP,LPS, and D-Lactate levels in critically ill patients with AGI admitted to the ICU. The primary outcome was the persistent intestinal failure, defined as AGI grades III–IV on day 3 after ICU admission. Multivariate logistic regression was used to identify independent risk factors for persistent intestinal failure, and an XGBoost model was applied to assess the relative importance of predictors for persistent intestinal failure. In addition, we performed mediation analysis to evaluate the mediating role of cytokines in the association between intestinal permeability (D-Lactate) and persistent intestinal failure. Results: 116 patients were included in the final analysis. On day 1 after ICU admission, levels of plasma biomarkers (IL-6, IL-10, TNF-α, I-FABP, LPS, and D-Lactate) were significantly higher in the AGI III-IV group compared with the AGI I-II group. These biomarkers showed a consistent decreasing trend from day 2 to day 5. Multivariate logistic regression identified IL-6, IL-10, D-Lactate and SOFA score as independent predictors of persistent intestinal failure. Using the XGBoost algorithm, we determined the relative importance for predicting persistent intestinal failure on day 3 of ICU admission. In descending order, the key predictors were IL‑6 (D1), IL‑10 (D1), D‑Lactate (D1), SOFA score, and gender. Mediation analysis showed that IL‑6, IL‑10, and TNF‑α partially mediated the association between D‑lactate levels and persistent intestinal failure. The respective proportions of their mediating effects were 73.3% for IL-6, 52.1% for IL-10, and 30.1% for TNF-α. Conclusions: In critically ill patients with AGI, the levels of cytokines on day 1 after ICU admission were positively associated with persistent intestinal failure during the early acute phase. Cytokines may partially mediate the relationship between intestinal injury and progression to persistent intestinal failure. Controlling the inflammatory response may represent a potential therapeutic strategy for acute gastrointestinal injury. Trial registration: Chinese Clinical Trial Registry, February 21, 2022. (Registration ID: ChiCTR2200056858).
Keywords: Acute gastrointestinal injury, Critical Illness, Cytokines, D-lactate, Intensive Care Unit, persistent intestinal failure
Received: 09 Sep 2025; Accepted: 12 Feb 2026.
Copyright: © 2026 Li, Wang, Ke, Li, Bao, Zhang, Li and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Hongxiang Li
Dong Zhang
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