Early immune system alterations in patients with septic shock

Abstract

This study aims to investigate the early changes in the immune systems of patients with septic shock. A total of 243 patients with septic shock were included in this study. The patients were classified as survivors (n = 101) or nonsurvivors (n = 142). Clinical laboratories perform tests of the immune system's function. Each indicator was studied alongside healthy controls (n = 20) of the same age and gender as the patients. A comparative analysis of every two groups was conducted. Univariate and multivariate logistic regression analyses were performed to identify mortality risk factors that are independent of one another. In septic shock patients, neutrophil counts, infection biomarkers (C-reactive protein, ferritin, and procalcitonin levels), and cytokines (IL-1β, IL-2R, IL-6, IL-8, IL-10, and TNF-α) increased significantly. Lymphocyte and their subset counts (T, CD4+ T, CD8+ T, B, and natural killer cell counts), lymphocyte subset functions (the proportions of PMA/ionomycin-stimulated IFN-γ positive cells in CD4+ T cells), immunoglobulin levels (IgA, IgG, and IgM), and complement protein levels (C3 and C4) decreased significantly. Compared to survivors, nonsurvivors had higher levels of cytokines (IL-6, IL-8, and IL-10) but lower levels of IgM, complement C3 and C4, and lymphocyte, CD4+, and CD8+ T cell counts. Low IgM or C3 concentrations and low lymphocyte or CD4+ T cell counts were independent risk factors for mortality. These alterations should be considered in the future development of immunotherapies aimed at treating septic shock.

Keywords: cytokine; immune system; immunoglobulin; lymphocyte; sepsis; septic shock.

Figure 1

Alterations in blood routine and infection biomarkers in patients with septic shock. Neutrophil counts (A), lymphocyte counts (B), monocyte counts (C), C-reactive protein levels (D), ferritin levels (E), and procalcitonin levels (F) were compared among healthy controls, survivors, and nonsurvivors. The shaded region represents the normal value range. The proportions of patients whose test results are above the upper limit of the normal range (A, C–F) or below the lower limit of the normal range (B) are shown on the x-axis.

Figure 2

Alterations of cytokines in patients with septic shock. The levels of IL-1 β (A), IL-2R (B), IL-6 (C), IL-8 (D), IL-10 (E), and TNF- α (F) were compared among healthy controls, survivors, and nonsurvivors. The shaded region represents the normal value range. The proportions of patients whose test results are above the upper limit of the normal range are shown on the x-axis (A–F).

Figure 3

Fluctuations of serum immunoglobulin and complement levels in patients with septic shock. The levels of IgA (A), IgG (B), IgM (C), C3 (D), and C4 (E) were compared among healthy controls, survivors, and nonsurvivors. The shaded region represents the normal value range. The proportions of patients whose test results are below the lower limit of the normal range are shown on the x-axis (A–E).

Figure 4

Changes of lymphocyte subset counts and CD4⁺/CD8⁺ ratios in septic shock patients. The counts of T cells (A), CD4⁺ T cells (B), CD8⁺ T cells (C), B cells (D), Natural killer (NK) cells (E), and CD4⁺/CD8⁺ ratios (F) were compared among healthy controls, survivors, and nonsurvivors. The shaded region represents the normal value range. The proportions of patients whose test results are below the lower limit of the normal range are shown on the x-axis (A–F).

Figure 5

Changes in lymphocyte functions in patients with septic shock. The proportions of PMA/ionomycin-stimulated IFN-γ positive cells in CD4⁺ T cells (A), CD8⁺ T cells (B), and Natural killer (NK) cells (C) were compared among healthy controls, survivors, and nonsurvivors. The shaded region represents the normal value range. The proportions of patients whose test results are below the lower limit of the normal range are shown on the x-axis (A–C).