# Endogenous IL-7 Variation in Relation to Lymphocyte Subtypes in Septic Patients

## TL;DR

This study examines how IL-7 levels in septic patients relate to different types of lymphocytes and finds that IL-7 is not a reliable biomarker for immune balance in sepsis.

## Contribution

The study provides new insights into the relationship between IL-7 and lymphocyte subtypes in sepsis survivors and non-survivors.

## Key findings

- IL-7 levels showed negative correlations with NKT cells in sepsis survivors on day 1.
- In non-survivors, IL-7 positively correlated with B cells on day 1.
- IL-7 lacked sufficient sensitivity and specificity as a biomarker for immune balance in sepsis.

## Abstract

Background and Objectives: Sepsis triggers a complex immune response, disrupting the balance between pro- and anti-inflammatory signals and causing widespread immune cell apoptosis. Interleukin 7 (IL-7) is emerging as one of the most promising immunoadjuvants to boost host immunity during the immunosuppressive phase of the disorder. This study aimed to investigate the dynamics of endogenous plasma levels of IL-7 during sepsis and septic shock, correlating its levels with lymphopenia and various lymphocyte subtypes, including CD4+ and CD8+ T cells, B cells, and natural killer T cells (NKT), in both survivors and non-survivors. Materials and Methods: This prospective observational study included 87 critically ill patients. We categorized the patients into four subgroups based on their diagnosis (sepsis or septic shock) and survival status (survivors and non-survivors). The parameters were monitored on day 1 (when sepsis was diagnosed according to the Sepsis-3 Consensus) and again on day 5. Eighty-two healthy volunteers were included as a control group to establish the cut-off values for IL-7. Results: Statistical analysis revealed a significant difference in median values between days 1 and 5 for lymphocytes (p = 0.01) and NKT cells (p = 0.01), observed only in sepsis survivors. In the group of sepsis survivors, we observed a negative correlation between IL-7 levels and NKT cells but only on day 1. Additionally, we identified negative correlations between Th cells (CD4+) and Tc cells (CD8+) on both day 1 and day 5. In the group of sepsis non-survivors, we observed a positive correlation between IL-7 and B cells (CD19+) but only on day 1. We also identified a negative correlation between Th cells (CD4+) and Tc cells (CD8+) on day 1. In the group of septic shock survivors, we did not observe any correlation between IL-7 levels and other parameters studied on day 1 or day 5. We identified a negative correlation between Th cells (CD4+) and Tc cells (CD8+) on both day 1 and day 5, a negative correlation between Th cells (CD4+) and NKT cells on both day 1 and day 5, and a positive correlation between Th cells (CD4+) and B cells (CD19+) on day 1. In the group of septic shock non-survivors, we did not observe any correlation between IL-7 and other parameters studied. Conclusions: Determining the IL-7 plasmatic value every five days did not demonstrate the necessary sensitivity and specificity as a biomarker to accurately assess each patient’s immune balance. Endogenous IL-7 levels appear inadequate to overcome the immunosuppressive environment induced by sepsis.