Jesús F Bermejo-Martin1, David Andaluz-Ojeda2, Raquel Almansa3, Francisco Gandía4, Jose Ignacio Gómez-Herreras5, Esther Gomez-Sanchez6, María Heredia-Rodríguez7, Jose Maria Eiros8, David J Kelvin9, Eduardo Tamayo10. 1. Infection and Immunity Medical Investigation Unit (IMI), Hospital Clínico Universitario de Valladolid, SACYL/IECSCYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain; Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain. Electronic address: jfbermejo@saludcastillayleon.es. 2. Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain; Servicio de Medicina Intensiva, Hospital Clínico Universitario de Valladolid, SACYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain. Electronic address: dandaluz@saludcastillayleon.es. 3. Infection and Immunity Medical Investigation Unit (IMI), Hospital Clínico Universitario de Valladolid, SACYL/IECSCYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain; Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain. Electronic address: ralmansa@saludcastillayleon.es. 4. Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain; Servicio de Medicina Intensiva, Hospital Clínico Universitario de Valladolid, SACYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain. Electronic address: fgandia@saludcastillayleon.es. 5. Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain; Servicio de Anestesiología y Reanimación, Hospital Clínico Universitario de Valladolid, SACYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain. Electronic address: jgomez012001@yahoo.es. 6. Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain; Servicio de Anestesiología y Reanimación, Hospital Clínico Universitario de Valladolid, SACYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain. Electronic address: esthergzam@hotmail.com. 7. Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain; Servicio de Anestesiología y Reanimación, Hospital Clínico Universitario de Valladolid, SACYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain. Electronic address: maria_her_05@hotmail.com. 8. Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain. Electronic address: eiros@med.uva.es. 9. Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, 200 Elizabeth Street, Toronto, ON M5G 2C4, Canada; Sezione di Microbiologia Sperimentale e Clinica, Dipartimento di Scienze Biomediche, Universita' degli Studi di Sassari, Piazza Università, 21, 07100 Sassari SS, Italy; International Institute of Infection and Immunity, Shantou University Medical College, 22 Xinling Road, Shantou, 515041 Guangdong Province, PR China. Electronic address: dkelvin@jidc.org. 10. Grupo de Investigación Biomédica en Cuidados Críticos (BioCritic), Hospital Clínico Universitario de Valladolid, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain; Servicio de Anestesiología y Reanimación, Hospital Clínico Universitario de Valladolid, SACYL, Avenida Ramón y Cajal, 3, 47005 Valladolid, Spain. Electronic address: eduardo.tamayo@uva.es.
Abstract
OBJECTIVES: Immunological dysregulation is now recognised as a major pathogenic event in sepsis. Stimulation of immune response and immuno-modulation are emerging approaches for the treatment of this disease. Defining the underlying immunological alterations in sepsis is important for the design of future therapies with immuno-modulatory drugs. METHODS: Clinical studies evaluating the immunological response in adult patients with Sepsis and published in PubMed were reviewed to identify features of immunological dysfunction. For this study we used key words related with innate and adaptive immunity. RESULTS: Ten major features of immunological dysfunction (FID) were identified involving quantitative and qualitative alterations of [antigen presentation](FID1), [T and B lymphocytes] (FID2), [natural killer cells] (FID3), [relative increase in T regulatory cells] (FID4), [increased expression of PD-1 and PD-ligand1](FID5), [low levels of immunoglobulins](FID6), [low circulating counts of neutrophils and/or increased immature forms in non survivors](FID7), [hyper-cytokinemia] (FID8), [complement consumption] (FID9), [defective bacterial killing by neutrophil extracellular traps](FID10). CONCLUSIONS: This review article identified ten major features associated with immunosuppression and immunological dysregulation in sepsis. Assessment of these features could help in utilizing precision medicine for the treatment of sepsis with immuno-modulatory drugs.
OBJECTIVES: Immunological dysregulation is now recognised as a major pathogenic event in sepsis. Stimulation of immune response and immuno-modulation are emerging approaches for the treatment of this disease. Defining the underlying immunological alterations in sepsis is important for the design of future therapies with immuno-modulatory drugs. METHODS: Clinical studies evaluating the immunological response in adult patients with Sepsis and published in PubMed were reviewed to identify features of immunological dysfunction. For this study we used key words related with innate and adaptive immunity. RESULTS: Ten major features of immunological dysfunction (FID) were identified involving quantitative and qualitative alterations of [antigen presentation](FID1), [T and B lymphocytes] (FID2), [natural killer cells] (FID3), [relative increase in T regulatory cells] (FID4), [increased expression of PD-1 and PD-ligand1](FID5), [low levels of immunoglobulins](FID6), [low circulating counts of neutrophils and/or increased immature forms in non survivors](FID7), [hyper-cytokinemia] (FID8), [complement consumption] (FID9), [defective bacterial killing by neutrophil extracellular traps](FID10). CONCLUSIONS: This review article identified ten major features associated with immunosuppression and immunological dysregulation in sepsis. Assessment of these features could help in utilizing precision medicine for the treatment of sepsis with immuno-modulatory drugs.
Authors: Djillali Annane; Lamia Ouanes-Besbes; Daniel de Backer; Bin DU; Anthony C Gordon; Glenn Hernández; Keith M Olsen; Tiffany M Osborn; Sandra Peake; James A Russell; Sergio Zanotti Cavazzoni Journal: Intensive Care Med Date: 2018-06-04 Impact factor: 17.440
Authors: Raquel Almansa; Leonor Nogales; Marta Martín-Fernández; Montse Batlle; Esther Villareal; Lucia Rico; Alicia Ortega; Guillermo López-Campos; David Andaluz-Ojeda; Paula Ramírez; Lorenzo Socias; Luis Tamayo; Jordi Vallés; Jesús F Bermejo-Martín; Ignacio Martín-Loeches Journal: Ann Transl Med Date: 2018-11