AUTHOR=Rackov Gorjana , Shokri Rahman , De Mon Melchor Álvarez , Martínez-A. Carlos , Balomenos Dimitrios 

TITLE=The Role of IFN-β during the Course of Sepsis Progression and Its Therapeutic Potential

JOURNAL=Frontiers in Immunology

VOLUME=Volume 8 - 2017

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.00493

DOI=10.3389/fimmu.2017.00493

ISSN=1664-3224

ABSTRACT=Sepsis is a complex biphasic syndrome characterized by both pro- and anti-inflammatory immune states. Whereas early sepsis mortality is caused by an acute, deleterious pro-inflammatory response, the second sepsis phase is governed by acute immunosuppression, which predisposes patients to long-term risk for life-threatening secondary infections.  Despite extensive basic research and clinical trials, there is to date no specific therapy for sepsis, and mortality rates are on the rise.  Although IFN- is one of the most-studied cytokines, its diverse effects are not fully understood.  Depending on the disease or type of infection, it can have beneficial or detrimental effects.  As IFN- has been used successfully to treat diverse diseases, emphasis has been placed on understanding the role IFN- in sepsis. Analyses of mouse models of septic shock attribute a proinflammatory role to IFN- in sepsis development. As anti-inflammatory treatments in humans with antibodies to TNF- or IL1- resulted disappointing, cytokine modulation approaches were discouraged and neutralization of IFN- has not been pursued for sepsis treatment.  In the case of patients with delayed sepsis and immunosuppression, there is a debate as to whether the use of specific cytokines would restore the deactivated immune response.  Recent reports show an association of low IFN- levels with the hyporesponsive state of monocytes from sepsis patients and after endotoxin tolerance induction. These data, discussed here, project a role for IFN- in restoring monocyte function and reversing immunosuppression, and suggest IFN -based additive immunomodulatory therapy.  The dichotomy in putative therapeutic approaches, involving reduction or an increase in IFN- levels, mirrors the contrasting nature of the early hyperinflammatory state and the delayed immunosuppression phase.