Biomarkers of early sepsis may be correlated with outcome

Abstract

Background: Sepsis causes high mortality, and the mortality due to secondary infections is even higher. No studies to date have investigated the time from the primary infection to death due to a secondary infection; similarly, the factors that are significantly different in sepsis survivors relative to non-survivors or in severe sepsis patients who suffered a late death relative to those who recover have not been explored. We hypothesized that patients who survive sepsis have a weaker pro-inflammatory response than those who do not and that the mid-term survivors (which acquire secondary infections) would have a pronounced anti-inflammatory response (making them susceptible to infection); this hypothesis was verified in this study.

Methods: We examined 24 patients with severe sepsis; the patients were subdivided by outcome into early death (n=5), mid-term survival (survival through severe sepsis but death within six months or continued hospitalization for six months, n=6), and long-term survival (recovery and survival for more than six months, n=13) groups. The levels of CD3+, CD4+, CD8+, and CD19+ lymphocytes were analyzed by flow cytometry, and the plasma levels of carbonic anhydrase IX (CA IX), MCP-1, IL-6, IL-7, IL-8, and IL-10 were measured by ELISA on days 0, 1, 2, and 3. A statistical comparison of the variables in the groups was conducted using a mixed model.

Results: The plasma levels of MCP-1, IL-6, and IL-8 in early death and survivors were significantly different, and all had p values<0.01. The plasma levels of MCP-1, IL-6, and IL-8 were also significantly different in mid-term survivors and long-term survivors, with p values of <0.01, 0.04, and <0.01, respectively.

Conclusions: Our data support the hypothesis that survivors have a weaker pro-inflammatory response than non-survivors, but the mid-term survivors did not have a more pronounced anti-inflammatory response. The levels of pro-inflammatory cytokines in the mid-term and long-term survivors were significantly different.

Figure 1

Flow chart of the cases included in this study.

Figure 2

Comparisons of lymphocyte subpopulations between the death and survival groups (2A, 2C, 2E, and 2G) and between the mid-term and long-term survival groups (2B, 2D, 2F, and 2H). The mean ± standard error of each group at each time point are shown; the subpopulation frequencies are LOG10 transformed. The differences between the groups were considered to be significant when p < 0.05. CA: carbonic anhydrase.

Figure 3

Comparisons of CA IX, MCP-1, IL-6, IL-7, IL-8, and IL-10 between death and survival (3A, 3C, 3E, 3G, 3I, and 3K) and between mid-term survival and long-term survival groups (3B, 3D, 3F, 3H, 3J and 3L). The mean ± standard error of each group at each time point are presented in LOG10 transformation. The difference between groups was considered significant with p < 0.05. CA: carbonic anhydrase, MCP: monocyte chemoattractant protein, IL: interleukin.