INIGEM   23989
INSTITUTO DE INMUNOLOGIA, GENETICA Y METABOLISMO
Unidad Ejecutora - UE
artículos
Título:
Immune dysfunction in cirrhosis: Distinct cytokines phenotypes according to cirrhosis severity
Autor/es:
MELISA DIRCHWOLF ; ARIEL PODHORZER ; MONICA MARINO ; CAROLINA SHULMAN; MARIANO CARTIER; MOIRA ZUNINO; SILVIA PAZ; ALBERTO MUÑOZ; ANDREA BOCASSI; JUAN GIMENEZ; LUCÍA DI PIETRO; GUSTAVO ROMERO; HUGO FAINBOIM; LEONARDO FAINBOIM
Revista:
CYTOKINE.
Editorial:
ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD
Referencias:
Lugar: Amsterdam; Año: 2015 vol. 77 p. 14 - 25
ISSN:
1043-4666
Resumen:
Background/objectives: Cirrhosis associated immune dysfunction has been proposed to switch from a proinflammatoryphenotype in stable cirrhosis to an immunodeficient one in patients with decompensatedcirrhosis and acute-on-chronic liver failure. The aim of the present study was to compare serum cytokinelevels between healthy patients, stable cirrhosis, and decompensated cirrhotic patients with and withoutdevelopment of acute-on-chronic liver failure (ACLF); and to explore whether any of the measuredcytokines is associated with cirrhosis severity and prognosis in ACLF patients.Methods: Patients were enrolled from October 2013 to May 2014 in two hospitals located in BuenosAires. Cirrhotic patients with an acute decompensating event were enrolled accordingly to the developmentof ACLF defined by the CANONIC study group. There were two control groups: healthy subjects(n = 14) and stable cirrhotic patients (n = 14). Demographic, clinical and biochemical data were obtained.Seventeen cytokines were measured using Bio-Plex Pro Human Cytokine 17-plex Assay.Results: Of the 49 decompensated cirrhotic patients enrolled, 18 (36.7%) developed ACLF. Leukocyte count,MELD score at admission, Clif-SOFA at admission and day 7 were significantly higher in the ACLF group(p = 0.046, p < 0.001, p < 0.001, p < 0.001 respectively) as well as short-term mortality (p < 0.001)compared to stable and decompensated cirrhotic patients. In comparison with healthy controls, stablecirrhotic and decompensated cirrhotic patients showed increased levels of pro-inflammatory andanti-inflammatory cytokines: IL-6, IL-7, IL-8, IL-10, IL 12, and TNF-a. Decompensated cirrhotic patientswith the development of ACLF showed a significant decrease of IL-7, IL-10, IL-12, TNF-a, MCP-1 andIFN-c, but a sustained response of IL-6 and IL-8. When evaluating cirrhosis severity, IL-6 and IL-8correlated positively with MELD score, whereas only IL-6 correlated positively with Clif-SOFA score atday 7; IL-2 correlated negatively with Clif-SOFA at admission. In comparison with all scores, leukocytecount showed positive correlation and IFN-c negative correlation with disease severity. When evaluatingsurvival, only MELD and Clif-SOFA scores had a significant association with mortality.