Abstract
Lymphopenia and functional defects in lymphocytes may impact the prognosis in patients with critical illness or sepsis. Therefore, we prospectively analyzed peripheral blood leukocytes from 63 healthy volunteers, 50 non-critically ill standard care (SC) patients with infections, and 105 intensive care unit (ICU) patients (52 with sepsis, 53 without sepsis) using flow cytometry. Compared to healthy volunteers, SC and ICU patients showed significant leukocytosis, especially in sepsis, while lymphocyte numbers were significantly decreased. All major lymphocyte populations (B, T, and natural killer (NK) cells) decreased in ICU patients. However, we observed a relative reduction of T cells, alongside decreased CD8+ T cells, in critically ill patients, independent of sepsis. High absolute T cell counts (>0.36/nL) at ICU admission were associated with a significantly reduced mortality, independent of patient’s age. Moreover, patients that survived ICU treatment showed dynamic changes within 48 h towards restoration of lymphopenia and T cell depletion, while non-surviving patients failed to restore lymphocyte counts. In conclusion, the flow-cytometric analysis of peripheral blood revealed striking changes in circulating lymphocyte subsets in critically ill patients, independent of sepsis. Lymphopenia and T cell depletion at ICU admission were associated with increased mortality, supporting their relevance as predictive biomarkers and potential therapeutic targets in intensive care medicine.
Highlights
Inappropriate systemic inflammation is a key characteristic in critically ill medical patients admitted to the intensive care unit (ICU) [1], especially in patients with sepsis [2]
We prospectively enrolled 63 healthy controls (HC), 50 standard care (SC) patients with ongoing infection diagnosed less than 24 h before, and 105 intensive care unit (ICU) patients submitted to the ICU less than 24 h before (Table 1), in order to conduct a detailed flow-cytometric analysis of circulating leukocytes
Patients in SC or ICU wards showed a significant increase in leukocytes (Figure 1A), which was expectedly pronounced in critically ill patients with sepsis (Table 1)
Summary
Inappropriate systemic inflammation is a key characteristic in critically ill medical patients admitted to the intensive care unit (ICU) [1], especially in patients with sepsis [2]. While leukocytes and systemic cytokines are highly prevalent during the onset of sepsis [5], granulocytes have an immature phenotype that suppresses adaptive immunity (oftentimes termed “myeloid-derived suppressor cells”) [5]. Because of this immune-suppressive myeloid phenotype, lymphocytes likely upregulate markers of cell exhaustion [6] and are unable to mount proper cytokine responses [7]. The in-depth understanding of immune pathogenesis may offer novel, tailored therapeutic interventions in intensive care medicine [10]
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