title: Rethinking the immune properties of bilirubin in viral hepatitis: from bench to bedside.
abstract: Communication between the immune system and metabolic components can be exemplified by the process of heme catabolism. The immunomodulatory functions of the enzymes, substrates and active products related to catabolism of the heme group have been extensively studied. Bilirubin (BR), the final breakdown product of heme, is primarily considered to be a toxic waste product but has recently been considered to be an immunomodulatory metabolite. Through mechanisms that include intracellular signaling and transcriptional control, BR affects those immune cell functions that regulate cell proliferation, differentiation and apoptosis. During the pathogenesis of viral hepatitis, the heme degradation pathway is disrupted, resulting in changes to normal BR concentrations. These alterations have been previously studied mainly as a consequence of the infection. However, little is known about the potential immunomodulatory role played by BR in the development of infectious hepatocellular diseases. Differences in BR levels in the context of viral hepatitis are likely to provide important insights into the metabolite-mediated mechanisms controlling the immune responses underlying both the long-term persistence of hepatitis C virus (HCV) infection and the resolution of hepatitis A virus (HAV) infection during the acute phase. In this review, the cross-talk between heme catabolism and immune function is described in detail. Special emphasis is given to discoveries that hold promise for identifying immunologic features of metabolic products in the resolution of viral diseases.
authors.affiliation: Unidad de Inmunovirología, Servicio de Biología Molecular en Medicina, Hospital Civil de Guadalajara 'Fray Antonio Alcalde' , Guadalajara, Mexico ; Departamento de Biología Molecular, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara , Guadalajara, Mexico.
authors.forename: Karla F
authors.initials: KF
authors.lastname: Corral-Jara
authors.affiliation: Unidad de Inmunovirología, Servicio de Biología Molecular en Medicina, Hospital Civil de Guadalajara 'Fray Antonio Alcalde' , Guadalajara, Mexico ; Departamento de Fisiologia, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara , Guadalajara, Mexico.
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Trujillo-Ochoa
authors.affiliation: Departamento de Medicina Veterinaria, Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara , Guadalajara, Mexico.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Realpe
authors.affiliation: Servicio de Biología Molecular en Medicina, Hospital Civil of Guadalajara 'Fray Antonio Alcalde' , Guadalajara, Mexico ; Departamento de Clínicas Médicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara , Guadalajara, Mexico.
authors.forename: Arturo
authors.initials: A
authors.lastname: Panduro
authors.affiliation: Departamento de Biología Molecular, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara , Guadalajara, Mexico ; Servicio de Biología Molecular en Medicina, Hospital Civil of Guadalajara 'Fray Antonio Alcalde' , Guadalajara, Mexico.
authors.forename: Sonia
authors.identifier: 0000-0001-7061-6634
authors.initials: S
authors.lastname: Roman
authors.affiliation: Unidad de Inmunovirología, Servicio de Biología Molecular en Medicina, Hospital Civil de Guadalajara 'Fray Antonio Alcalde' , Guadalajara, Mexico ; Departamento de Fisiologia, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara , Guadalajara, Mexico.
authors.forename: Nora A
authors.initials: NA
authors.lastname: Fierro