Context and objectives
Hepatic insufficiency syndromes are characterized by a deregulated immune response leading to immune paralysis. Adrenomedullin (ADM) is a powerful vasodilator and immunoregulator. This study aimed to explore the role of the ADM in liver insufficiency, emitting the hypothesis that there is a prejudicial imbalance between ADM and the adrenomedulline liaison protein (AMBP) 1 which promotes a monocyte / macrophages switch against a phenotype and a pro-production function.
Methods
Consecutive patients suffering from acute hepatic insufficiency (ALF), acute hepatic insufficiency on chronic (ACLF) and decompensated cirrhosis, as well as healthy witnesses (HC) were included between April 2020 and June 2024. Mononuclear / mononuclear blood cells were isolated and used for sequencing and cell culture. ADM and AMBP1 were measured by immuno-enzymatic test.
Results
Fifty-four patients with ALF, 25 with ACLF, 9 with decompensated cirrhosis and 16 with HC were included. The expression ADM in isolated monocytes has been increased in the ALF (change of log = 5.88, p = 0.000216413) and ACLF (change of log folding = 4.62, p = 0.00057122) compared to HC. The plasma concentration of ADM was higher in the ALF (1,684 ± 1,156 pg / ml) vs ACLF (836.1 ± 765.2 pg / ml) and HC (164.8 ± 62.73 pg / ml). AMBP1 has been significantly reduced in the ALF (59.27 ± 44 µg / ml) compared to the ACLF (126.3 ± 72.23 µg / ml) and HC (252.8 ± 159.7 µg / ml) (p <0.0001, ALF vs HC). The treatment with LPS increased the concentration of ADM in the supernatant of the mononuclear cells of the peripheral blood (ALF N = 6; 561.4 ± 1,038 pg / ml vs 259.2 ± 213.7 pg / ml, ACLF n = 4; 3202 ± 491.2 vs 1,757 ± 1.689 pg / ml). The percentage of CD14+ The cells expressing the tyrosine sea kinase were reduced after culture with the LPS (2.077 ± 0.87%); However, co-culture with ADM 100 NM restored the phenotype (3.852 ± 1.063%).
Conclusions
The ADM is increased in acute liver insufficiency syndromes (ALF and ACLF), and AMBP1 is, on the contrary, reduced, reflecting the severity of the disease expressed by the sofa of the sofa. The ADM affects the function of monocytes, increasing the MERTK after stimulation of LPS and promoting a pro-restaurant and anti-inflammatory phenotype. Other studies are necessary to fully understand how to modulate this path as a possible therapeutic target and restore the function of monocytes.
