Lesley Doughty1. 1. Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Abstract
PURPOSE OF REVIEW: This review is being published to update the literature on the function of the adaptive immune system in critical illness, specifically sepsis and acute lung injury. We have focused on the role of T cells in these syndromes. RECENT FINDINGS: The adaptive immune response becomes dysfunctional during sepsis and acute lung injury in very similar ways. Many of the abnormalities contribute to morbidity and mortality. Immunoparalysis captures the breadth of the dysfunction in that T-cell functions are broadly suppressed after the early proinflammatory stages of illness. Lymphocyte apoptosis, decreased antigen responsiveness, decreased and altered cytokine expression, upregulation of inhibitory molecules, and expansion of the suppressive regulatory T-cell population are mechanisms involved. Each of these abnormalities can be reversed with improvement in experimental outcomes. SUMMARY: Immunoparalysis of the adaptive immune system occurs in sepsis and acute lung injury, and is critical to the outcome. Blocking the inhibited pathways and immunostimulant cytokines improved lymphocyte function and outcome. Many such blocking agents are already effective for other diseases and could be used for immunoparalysis. Unfortunately, there is no diagnostic marker yet. In order to provide the right therapy at the right time, advancements in immunomonitoring are necessary.
PURPOSE OF REVIEW: This review is being published to update the literature on the function of the adaptive immune system in critical illness, specifically sepsis and acute lung injury. We have focused on the role of T cells in these syndromes. RECENT FINDINGS: The adaptive immune response becomes dysfunctional during sepsis and acute lung injury in very similar ways. Many of the abnormalities contribute to morbidity and mortality. Immunoparalysis captures the breadth of the dysfunction in that T-cell functions are broadly suppressed after the early proinflammatory stages of illness. Lymphocyte apoptosis, decreased antigen responsiveness, decreased and altered cytokine expression, upregulation of inhibitory molecules, and expansion of the suppressive regulatory T-cell population are mechanisms involved. Each of these abnormalities can be reversed with improvement in experimental outcomes. SUMMARY: Immunoparalysis of the adaptive immune system occurs in sepsis and acute lung injury, and is critical to the outcome. Blocking the inhibited pathways and immunostimulant cytokines improved lymphocyte function and outcome. Many such blocking agents are already effective for other diseases and could be used for immunoparalysis. Unfortunately, there is no diagnostic marker yet. In order to provide the right therapy at the right time, advancements in immunomonitoring are necessary.
Authors: Joseph A Carcillo; Bradley Podd; Rajesh Aneja; Scott L Weiss; Mark W Hall; Timothy T Cornell; Thomas P Shanley; Lesley A Doughty; Trung C Nguyen Journal: Pediatr Crit Care Med Date: 2017-03 Impact factor: 3.624