Study on immune status alterations in patients with sepsis

Abstract

Sepsis, characterized by cytokine-mediated hyper-inflammation and a consistent decline in immune responsiveness, is associated with a high risk of death in the intensive care unit (ICU). Here, we for the first time investigated the changes in immune and inflammatory responses to understand the interactions between immune and inflammatory biomarkers and their association with patient outcomes. The cytokine and lymphocyte subset levels were analyzed in healthy donors (HD) and patients with sepsis upon admission to the ICU (D0), D3, D7, D14, and D28 using flow cytometry. The primary endpoint was mortality on day 90. The trends in lymphocyte subsets and cytokine levels in all patients (n = 47), HD (n = 27), and patient subgroups (surviving, n = 30; dead, n = 17) were analyzed using an independent sample t-test and principal component analysis. Age, steroids (steroids used > 48 h), secondary infection, acute heart failure, acute kidney injury, coagulopathy, hypohepatia, organ transplant and septic shock (when transferred to the ICU) were associated with mortality. Absolute lymphocyte counts and lymphocyte subsets levels were reduced in most patients with sepsis. The proportion of Tregs in the patients increased with disease progression and was associated with immunosuppression. In conclusion, sepsis downregulated adaptive immunity, and induced the transition of the patients to prolonged immune suppression. The study suggests that while cellular immunity recovered within 2 weeks of admission, humoral and innate immunity recovery takes longer. These findings may assist in developing appropriate therapeutic approaches to improve the immune responses in patients with sepsis.

Keywords: Cytokines; Immunosuppression; Lymphocyte subsets; Outcome; Sepsis.