Systemic inflammation and protease profile of Afro-Caribbean patients with sepsis

Abstract

Objectives: Sepsis is one of the leading causes of morbidity and mortality within the healthcare system and remains a diagnostic and therapeutic challenge. A major issue in the diagnosis of sepsis is understanding the pathophysiologic mechanism, which revolves around host immune system activation and dysregulated responses. African Americans are more likely to experience severe sepsis with higher mortality rates compared to the general population. This pilot study characterized multiple inflammatory markers and proteases in plasma of primarily African American and Afro-Caribbean patients with mild sepsis.

Methods: Plasma was collected from 16 healthy controls and 15 subjects presenting with sepsis, on admission, and again upon resolution of the signs of sepsis, defined as a resolution of sepsis criteria. Plasma samples were analyzed for cytokines, chemokines, and proteases using multiplex bead assays.

Results: Elevated levels of granulocyte colony-stimulating factor, interleukin-10, interleukin-15, interleukin-1 receptor antagonist, interleukin-8, interferon gamma-induced protein 10, monocyte chemoattractant protein-1, matrix metallopeptidase 12, and cathepsin S were identified in plasma from sepsis patients on admission compared to control subjects. Interleukin-6, interleukin-8, granulocyte colony-stimulating factor, and cathepsin S were reduced in sepsis patients upon clinical resolution of sepsis.

Conclusion: These findings profile the circulating inflammatory cytokines, chemokines, and proteases in African Americans and Afro-Caribbean patients during sepsis. The role of these targets in sepsis needs addressing in this patient population.

Keywords: Sepsis; blood inflammatory immune response; cathepsin; chemokines; cytokines.

Figure 1.

Plasma levels of G-CSF, IL-8, IL-6, and CTSS reduce following clinical resolution. (a) Luminex bead assays were performed for G-CSF, IL-10, IL-15, IL-1RA, IL-8, IP-10, MCP-1, IL-6, MMP-12, and CTSS on plasma from sepsis patients at the time of admission (Sepsis A) and following clinical resolution (Sepsis B). (b) Plasma levels of G-CSF, IL-8, IL-6, and CTSS from Sepsis A and B. Corresponding squares connected by a line to demonstrate trend for individual subjects. Concentrations are given in pg/mL of plasma. Data are presented as mean values and SD. Data were analyzed by D’Agostino and Pearson omnibus normality test and further analyzed by the Wilcoxon signed-rank test. p-values are shown comparing groups connected by a line.