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Reticuloendothelial activation and phenotypic alteration of peripheral monocytes with enhanced liver recruitment
Balakrishnan Vijayalekshmi1, Anita Choudhary1, Vijay Alexander2
1Wellcome Trust Research Laboratory, Division of Gastrointestinal Sciences, Christian Medical College, Vellore, India.
Background And Aim:
Monocytes and macrophages play a crucial role in the pathogenesis of acute liver failure (ALF). We aimed to study reticuloendothelial activation and its correlation with disease severity in commonly encountered yellow phosphorus (rodenticide)-induced hepatotoxicity patients. We also studied peripheral monocyte phenotype in a subset of patients.
Methods:
Reticuloendothelial activation markers were analyzed and correlated with disease severity score in a prospectively collected database of yellow phosphorus-related hepatoxicity patients between 2018 and 2021. In a prospective cohort of these patients and age-matched healthy controls, peripheral blood monocyte phenotyping was performed.
Results:
Reticuloendothelial activation markers were analyzed in 67 patients [Age: 23(12-64) years; median (range), men: 25, acute liver injury (ALI): 38, ALF: 29, model for end-stage liver disease (MELD) score: 28 (7-40)] of yellow phosphorus-induced hepatotoxicity. Serum ferritin (927; 10.3-34 807 ng/mL), sCD163 (4.59; 0.11-12.7 μg/mL), sCD25 (3050; 5.6-17 300 pg/mL) and plasma von Willebrand factor (423.5, 103-1106 IU/dL) were increased and showed significant correlation with liver disease severity assessed by MELD score (ρ = 0.29, ρ = 0.6, ρ = 0.56 and ρ = 0.46 respectively). Phenotyping and serum immune markers were performed in seven patients (M: 4; age: 27, 15-37 years; median, range; MELD score: 36, 21-40) and compared with eight healthy controls. Increase in classical monocytes and decrease in patrolling and intermediate monocyte subsets were observed in ALF cohort. HLA-DRlow CD163hi (immune exhaustion), CD64hi (immune complex-mediated response), and CCR2hi (liver homing) monocyte phenotype was noted.
Conclusion:
Altered peripheral monocyte phenotype with enhanced liver homing and macrophage activation, suggests important role of innate immune activation, and provides a potential therapeutic target, in yellow phosphorus-induced hepatotoxicity.
Insights
Yellow phosphorus (rodenticide) poisoning causes acute liver failure (ALF) by activating macrophages. This study found increased immune markers and altered monocyte phenotypes in patients, suggesting innate immune activation as a therapeutic target.
Area of Science:
- Immunology
- Hepatology
- Toxicology
Background:
- Monocytes and macrophages are key players in acute liver failure (ALF) pathogenesis.
- Yellow phosphorus (rodenticide) poisoning is a common cause of hepatotoxicity.
- Reticuloendothelial activation and monocyte phenotype alterations are implicated in ALF severity.
Purpose of the Study:
- To investigate reticuloendothelial activation markers and their correlation with disease severity in yellow phosphorus-induced hepatotoxicity.
- To analyze peripheral monocyte phenotypes in patients with yellow phosphorus-induced hepatotoxicity.
- To identify potential therapeutic targets for yellow phosphorus-induced hepatotoxicity.
Main Methods:
- Analysis of reticuloendothelial activation markers in 67 patients with yellow phosphorus-induced hepatotoxicity.
- Correlation of marker levels with the Model for End-Stage Liver Disease (MELD) score.
- Peripheral blood monocyte phenotyping in 7 patients and 8 healthy controls.
Main Results:
- Elevated serum ferritin, sCD163, sCD25, and plasma von Willebrand factor correlated significantly with MELD scores.
- Patients with acute liver failure exhibited increased classical monocytes and decreased patrolling/intermediate subsets.
- Observed monocyte phenotypes included immune exhaustion (HLA-DRlow CD163hi), immune complex response (CD64hi), and liver homing (CCR2hi).
Conclusions:
- Altered peripheral monocyte phenotypes and enhanced macrophage activation are evident in yellow phosphorus-induced hepatotoxicity.
- Innate immune activation plays a significant role in the pathogenesis of this condition.
- These findings suggest potential therapeutic targets for managing yellow phosphorus-induced liver injury.
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