TY - JOUR
T1 - Lymphopenia in sepsis—an acquired immunodeficiency?
AU - Finfer, Simon
AU - Venkatesh, Balasubramanian
AU - Hotchkiss, Richard S.
AU - Sasson, Sarah C.
N1 - Publisher Copyright:
© 2022 The Authors. Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of the Australian and New Zealand Society for Immunology, Inc.
PY - 2023/7
Y1 - 2023/7
N2 - Sepsis is a global health priority, yet effective host-directed targeted therapies have not been identified outside of the setting of coronavirus disease 2019 (COVID-19). Lymphopenia occurs in up to ~52% of patients with sepsis and is associated with a higher mortality at both 30 and 100 days. In COVID-19, the presence of lymphopenia correlates with intensive care unit admission, acute respiratory distress syndrome and death. The mechanisms underpinning lymphopenic sepsis remain unknown, and while high rates of lymphocyte apoptosis have been implicated, the relative contributions of cellular trafficking to inflamed tissues and reduction in lymphopoiesis require investigation. Further delineation of these underlying mechanisms holds the potential to open new avenues for the development of host-directed therapies in lymphopenic sepsis. These may include recombinant cytokines (e.g. interleukin-7), monoclonal antibodies (e.g. anti-interleukin-1, anti-programmed cell death protein 1) and small interfering RNA (e.g. targeting interleukin-10, transforming growth factor beta). Applying the frontier tools of translational cellular and genomic medicine to understand lymphopenia in the setting of critical infections holds the potential to significantly reduce the excessive global burden of sepsis.
AB - Sepsis is a global health priority, yet effective host-directed targeted therapies have not been identified outside of the setting of coronavirus disease 2019 (COVID-19). Lymphopenia occurs in up to ~52% of patients with sepsis and is associated with a higher mortality at both 30 and 100 days. In COVID-19, the presence of lymphopenia correlates with intensive care unit admission, acute respiratory distress syndrome and death. The mechanisms underpinning lymphopenic sepsis remain unknown, and while high rates of lymphocyte apoptosis have been implicated, the relative contributions of cellular trafficking to inflamed tissues and reduction in lymphopoiesis require investigation. Further delineation of these underlying mechanisms holds the potential to open new avenues for the development of host-directed therapies in lymphopenic sepsis. These may include recombinant cytokines (e.g. interleukin-7), monoclonal antibodies (e.g. anti-interleukin-1, anti-programmed cell death protein 1) and small interfering RNA (e.g. targeting interleukin-10, transforming growth factor beta). Applying the frontier tools of translational cellular and genomic medicine to understand lymphopenia in the setting of critical infections holds the potential to significantly reduce the excessive global burden of sepsis.
KW - Acquired immunodeficiency
KW - T cells
KW - immunodeficiency
KW - lymphopenia
KW - sepsis
UR - http://www.scopus.com/inward/record.url?scp=85144180332&partnerID=8YFLogxK
U2 - 10.1111/imcb.12611
DO - 10.1111/imcb.12611
M3 - Article
C2 - 36468797
AN - SCOPUS:85144180332
SN - 0818-9641
VL - 101
SP - 535
EP - 544
JO - Immunology and Cell Biology
JF - Immunology and Cell Biology
IS - 6
ER -