Interaction of inflammatory factors related to pulmonary infection and TLR4/NF-κB signaling pathway in patients with spontaneous intracerebral hemorrhage

Objective: To investigate the interaction of inflammatory factors related to pulmonary infection and the TLR4/NF-κB signaling pathway in patients with spontaneous intracerebral hemorrhage (ICH).

Methods: A total of 325 critically ill ICH patients treated in our hospital from May 2021 to February 2024 were selected for this study. Based on whether the patient developed a pulmonary infection during treatment, they were divided into the infection group (n = 86) and the non-infection group (n = 239). The distribution characteristics of pathogens were observed, and changes in serum and defensin, hs-CRP, IL-4, TLR4 mRNA, and NF-κB mRNA were compared. Pearson correlation analysis was used to analyze the relationship between serum defensin, inflammatory factors, and the TLR4/NF-κB signaling pathway. A logistic regression model was used to construct a combined prediction model with defensin, hs-CRP, IL-4, HMGB1, TLR4 mRNA, and NF-κB mRNA. ROC curves were drawn to analyze the area under the curve (AUC), sensitivity, and specificity of defensin, hs-CRP, IL-4, HMGB1, TLR4 mRNA, NF-κB mRNA, and the six combined parameters for predicting pulmonary infection in critically ill ICH patients.

Results: In 86 ICH patients with pulmonary infection, 94 strains of pathogens were isolated, with 28 (29.79 %) Gram-positive bacteria, 58 (61.70 %) Gram-negative bacteria, and 8 (8.51 %) fungi. The levels of defensin, hs-CRP, IL-4, HMGB1, TLR4 mRNA, and NF-κB mRNA in the infection group were significantly higher than those in the non-infection group (P < 0.05). Pearson correlation analysis showed that defensin, hs-CRP, IL-4, and HMGB1 were positively correlated with TLR4 mRNA and NF-κB mRNA (P < 0.05). ROC curve analysis showed that the AUC values for defensin, hs-CRP, IL-4, HMGB1, TLR4 mRNA, NF-κB mRNA, and the six combined parameters for predicting pulmonary infection were 0.789, 0.778, 0.690, 0.792, 0.741, 0.750, and 0.870, respectively.

Conclusion: The main pathogens causing pulmonary infection in critically ill ICH patients are Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Staphylococcus aureus, and Streptococcus hemolyticus. Defensin, hs-CRP, IL-4, HMGB1, and other indicators are influenced by the TLR4/NF-κB signaling pathway in patients with secondary pulmonary infection.