La interleucina-6 producida por hepatocitos modula el perfil inmunológico en ratones

Interleukin-6 (IL-6), which is a pleiotropic cytokine with both pro- and anti-inflammatory properties, exerts a great variety of functions in the organism. This protein plays a vital role in biologic processes such as haematopoiesis, the induction of the acute phase response, and liver regeneration, and it is a key regulator of the immune system. The synthesis of IL-6 is triggered by inflammatory conditions and this cytokine contributes to the intercellular communication among immune cells, regulating their activation, proliferation, and differentiation. Immune cells, endothelial cells and fibroblasts are considered the major source of IL-6, but recent studies have proven that hepatocytes, the main cells of the liver, are also capable of synthetizing and releasing IL-6 in response to inflammatory stimuli. Of note, the liver is an organ with a high density of immune cells in which a fine regulation of the immune response is crucial for the maintenance of homeostasis. Given the immunological importance of this organ, the aim of the present Degree Final Project was to perform a pilot study to determine whether the production of IL-6 by hepatocytes plays a role on the differentiation of immune cells in mice. To achieve this aim, we assessed the populations of a large variety of circulating myeloid and lymphoid immune cell subsets by multiparametric flow cytometry analysis at baseline and after exposure to an inflammatory insult such as lipopolysaccharide (LPS) administration, in control and in conditional knock-out mice with hepatocyte-specific IL-6 deficiency. All the evaluated cell populations were similar in control mice and hepatocyte IL-6 deficient mice at baseline. The administration of LPS induced significant alterations affecting numerous myeloid and lymphoid immune cell sub-populations that were mostly similar in control and in hepatocyte-specific IL-6 knock-out mice. Compared to control mice, hepatocyte-specific IL-6 knock-out mice showed, however, increased activated CD4 T cell sub-population at 24 hours after LPS administration. The results of the present preliminary study indicate that IL-6 produced by hepatocytes may have a specific effect on the regulation of the immune response to LPS, probably by reducing CD4 T cell activation or survival.