The Role of PD-1/PD-L1 and IL-7 in Lymphocyte Dynamics and Sepsis Progression: A Biomarker Study in Critically Ill Patients

Int J Mol Sci. 2024 Nov 24;25(23):12612. doi: 10.3390/ijms252312612.

Abstract

Sepsis pathophysiology involves a dysregulated immune response to infection, excessive inflammation, and immune paralysis. This study explores the relationships between cell death biomarkers (serum-soluble levels of programmed cell death protein 1 (PD-1), programmed death ligand 1 (PD-L1), and interleukin-7 (IL-7)) and the percentages of various lymphocyte subsets in relation to the severity and progression of sepsis. This prospective, observational study included 87 critically ill patients. We monitored parameters on days 1 (sepsis was diagnosed according to the Sepsis-3 Consensus) and 5. We established an IL-7 cutoff value of 1.94 pg/mL by comparing levels between a healthy control group and patients with sepsis (p < 0.0001). Lymphopenia was observed in all patients, with negative correlations between helper T lymphocytes and cytotoxic and B lymphocytes, and positive correlations involving cytotoxic lymphocytes across all groups. We found correlations between PD-1/PD-L1 and lymphocyte subsets. IL-7 showed a statistical correlation with PD-1 in non-survivors. Assessing lymphocyte levels shows potential as a biomarker for evaluating the progression of sepsis. Monitoring IL-7 levels could help assess survival, as low levels are associated with higher mortality risk. Monitoring IL-7 levels could help assess survival, as low levels are associated with higher mortality risk. Elevated PD-1/PD-L1 expression impairs costimulatory signalling, reducing T cell responses and lymphopenia, which increases the risk of nosocomial infections.

Keywords: CD19+ lymphocytes; CD4+ lymphocytes; CD8+ lymphocytes; IL-7; PD-1/PD-L1 axis; apoptosis; lymphopenia; natural killer lymphocytes; sepsis; septic shock.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • B7-H1 Antigen* / blood
  • B7-H1 Antigen* / metabolism
  • Biomarkers* / blood
  • Critical Illness*
  • Disease Progression
  • Female
  • Humans
  • Interleukin-7* / blood
  • Interleukin-7* / metabolism
  • Lymphocytes / immunology
  • Lymphocytes / metabolism
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor* / metabolism
  • Prospective Studies
  • Sepsis* / blood
  • Sepsis* / immunology
  • Sepsis* / metabolism

Substances

  • Interleukin-7
  • Programmed Cell Death 1 Receptor
  • B7-H1 Antigen
  • Biomarkers
  • CD274 protein, human
  • PDCD1 protein, human
  • IL7 protein, human