Ascitic fluid regulates the local innate immune response of patients with cirrhosis

• Published in: Journal of leukocyte biology Vol. 104; no. 4; pp. 833 - 841
• Main Authors: Nieto, Juan C., Perea, Lídia, Soriano, Germán, Zamora, Carlos, Cantó, Elisabet, Medina, Aina, Poca, Maria, Sanchez, Elisabet, Roman, Eva, Julià, Germà, Navarro, Ferran, Gely, Cristina, Alvarado, Edilmar A., Guarner, Carlos, Juarez, Cándido, Vidal, Sílvia
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.10.2018
• Subjects: Aged; Anti-Bacterial Agents - therapeutic use; Ascites; Ascites - etiology; Ascites - immunology; Ascitic fluid; Ascitic Fluid - cytology; Ascitic Fluid - immunology; Bacteria; Bacterial diseases; Bacterial Infections - complications; Bacterial Infections - drug therapy; Cirrhosis; Cytokines - metabolism; Down-regulation; E coli; Extracellular Traps - immunology; Female; Flow cytometry; Glucose - metabolism; Humans; Immune response; Immune system; Immunity, Innate; Inflammation; Inflammatory response; Innate immunity; Interleukin 1 receptor antagonist; Interleukin-1beta - metabolism; Interleukin-6 - metabolism; Interleukins; Lactoferrin; Lactoferrin - metabolism; Leukocytes (neutrophilic); Liver cirrhosis; Liver Cirrhosis - immunology; Liver diseases; Macrophages; Macrophages - immunology; Male; Middle Aged; Monocytes; Monocytes - immunology; NETosis; Neutrophils; Neutrophils - immunology; oxidative burst; Peritonitis; Peritonitis - complications; Peritonitis - drug therapy; Phenotypes; resistin; Resistin - metabolism; Respiratory Burst; Severity of Illness Index; spontaneous bacterial peritonitis; Tumor necrosis factor-α; Up-Regulation; resistin; oxidative burst; NETosis; spontaneous bacterial peritonitis
• ISSN: 0741-5400; 1938-3673; 1938-3673
• DOI: 10.1002/JLB.3A0218-072R

Ascitic neutrophils from cirrhotic patients with spontaneous bacterial peritonitis (SBP) exhibit an impaired oxidative burst that could facilitate bacterial infection. However, the influence of the cell‐free ascitic fluid of these patients on neutrophil function has not been investigated. To analyze this influence, we determined the ascitic levels of cytokines, resistin, and lactoferrin and their association with neutrophil function, disease severity score, and SBP resolution. We analyzed NETosis induction by microscopy and oxidative burst by the flow cytometry of healthy neutrophils cultured in ascitic fluid from cirrhotic patients with sterile ascites (SA) and with SBP before and after antibiotic treatment. Resistin, IL‐6, IL‐1 receptor antagonist, IL‐1β, and lactoferrin levels were measured in ascitic fluids and supernatants of cultured neutrophils and PBMCs by ELISA. Upon stimulation, healthy neutrophils cultured in SBP ascitic fluid produced lower NETosis and oxidative burst than those cultured in SA. Ascitic resistin levels were negatively correlated with NETosis, oxidative burst, and ascitic glucose levels; and positively correlated with the model for end‐stage liver disease score. After an E. coli or TNF‐α stimulus, neutrophils were the major resistin producers. Resistin indirectly reduced the oxidative burst of neutrophils and directly reduced the inflammatory phenotype of monocytes and TNF‐α production. Bacterial‐induced resistin production can down‐regulate the inflammatory response of macrophages and neutrophil function in ascitic fluid. Consequently, this down‐regulation may jeopardize the elimination of bacteria that translocate to ascitic fluid in patients with cirrhosis. Downregulation of the immune response of ascitic cells from cirrhotic patients can be induced by the content of ascitic fluid.