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Review
. 2024 Sep 20;28(1):315.
doi: 10.1186/s13054-024-05099-4.

Lymphopenia in sepsis: a narrative review

Zhibin Wang #  1 , Wenzhao Zhang #  2 , Linlin Chen #  2 , Xin Lu  2 , Ye Tu  3
Affiliations
Review

Lymphopenia in sepsis: a narrative review

Zhibin Wang et al. Crit Care. .

Abstract

This narrative review provides an overview of the evolving significance of lymphopenia in sepsis, emphasizing its critical function in this complex and heterogeneous disease. We describe the causal relationship of lymphopenia with clinical outcomes, sustained immunosuppression, and its correlation with sepsis prediction markers and therapeutic targets. The primary mechanisms of septic lymphopenia are highlighted. In addition, the paper summarizes various attempts to treat lymphopenia and highlights the practical significance of promoting lymphocyte proliferation as the next research direction.

Keywords: Immunotherapy; Lymphopenia; Mechanism; Sepsis.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Timeline of sepsis-induced lymphopenia. Half a century of research on the relevance and pathophysiology of lymphopenia to sepsis suggests the promise of therapeutic strategies targeting lymphopenia in sepsis immunomodulation
Fig. 2
Fig. 2
Increased apoptosis and impaired proliferation of lymphocytes contribute to sepsis-induced lymphopenia. TGF-β and catecholamine release or L-arginine depletion during sepsis enhance lymphocyte apoptosis. Reduced thymic output, bone marrow “void”, or decreased levels of thyroid hormones limit the effective proliferation of lymphocytes after the onset of septic lymphopenia. Immune checkpoints and inhibitory cells, including regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), induce apoptosis and impair proliferation
Fig. 3
Fig. 3
Cellular and molecular mechanisms of sepsis-induced lymphopenia. a Fas/FasL pathway, mitochondrial pathway, and endoplasmic reticulum stress-mediated apoptosis are all involved in sepsis-induced apoptosis of lymphocytes. b Reduced thymic output, impaired lymphoid progenitor cell generation, poor thymic homing, and insufficient peripheral homeostatic or antigen-driven proliferation combine to diminish lymphocyte proliferative capacity after sepsis
See this image and copyright information in PMC

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