Host Response Biomarkers in the Diagnosis of Sepsis: A General Overview

Abstract

Critically ill patients who display a systemic inflammatory response syndrome (SIRS) are prone to develop nosocomial infections. The challenge remains to distinguish as early as possible among SIRS patients those who are developing sepsis. Following a sterile insult, damage-associated molecular patterns (DAMPs) released by damaged tissues and necrotic cells initiate an inflammatory response close to that observed during sepsis. During sepsis, pathogen-associated molecular patterns (PAMPs) trigger the release of host mediators involved in innate immunity and inflammation through identical receptors as DAMPs. In both clinical settings, a compensatory anti-inflammatory response syndrome (CARS) is concomitantly initiated. The exacerbated production of pro- or anti-inflammatory mediators allows their detection in biological fluids and particularly within the bloodstream. Some of these mediators can be used as biomarkers to decipher among the patients those who developed sepsis, and eventually they can be used as prognosis markers. In addition to plasma biomarkers, the analysis of some surface markers on circulating leukocytes or the study of mRNA and miRNA can be helpful. While there is no magic marker, a combination of few biomarkers might offer a high accuracy for diagnosis.

Randomized Phase I Healthy Volunteer Study of UTTR1147A (IL‐22Fc): A Potential Therapy for Epithelial Injury

“…Danilenko, unpublished data) and notably, occurred in the absence of signs of inflammation, such as fever, leukocytosis, or vital sign changes. We also examined serum levels of IL‐1β, IL‐2, IL‐6, IL‐8, IL‐10, tumor necrosis factor‐α, and interferon‐γ, and cytokines associated with inflammatory responses ( Figure ) . Importantly, none of the cytokines demonstrated any dose‐dependent increases in response to UTTR1147A, corroborating observations that CRP increases were on‐target, dose‐dependent effects of UTTR1147A administration.…”

Thrombocytopenia is associated with a dysregulated host response in critically ill sepsis patients

“…Demographics, chronic comorbidities, and disease severity were not different between propensity matched groups (supplemental Table 1). As expected, 37,38 sepsis patients displayed a profound activation of the cytokine network, as reflected by elevated plasma levels of IL-6, IL-8, and IL-10 ( Figure 3). In the unmatched cohort, patients with thrombocytopenia presented with increased levels of IL-6, IL-8, and IL-10 (supplemental Table 2).…”

“…Considering that the release of host response biomarkers in sepsis often is proportional to disease severity, 37,38 we used propensity score matching to create groups with distinct platelet counts yet with comparable disease severity on ICU admission to determine the association between thrombocytopenia and the host response. For this, we used a logistic regression implemented in the R library MatchIt (version 2.4-21), including variables associated with disease severity and baseline variables that were different between groups or could be of influence on our parameter of interest or outcome.…”

“…As disease severity can strongly influence the release of host response biomarkers in sepsis, 37,38 we used propensity score matching to create groups with distinct platelet counts yet with comparable disease severity on ICU admission. Demographics, chronic comorbidities, and disease severity were not different between propensity matched groups (supplemental Table 1).…”

Natural Killer Cell Assessment in Peripheral Circulation and Bronchoalveolar Lavage Fluid of Patients with Severe Sepsis: A Case Control Study

“…Although a localized inflammatory response is needed for the clearance of infection, failure of anti-inflammatory mediators to control the inflammatory process can lead to endothelial dysfunction allowing further invasion of pathogens into host organs [6]. In addition, patients surviving the initial SIRS stage were discovered to frequently enter an immunosuppressive state during the later stage of sepsis, described as a compensatory anti-inflammatory response syndrome (CARS) [10,11]. CARS is a consequence of the body’s initial pro-inflammatory immune state during sepsis, leading to a defective adaptive immune response rendering patients susceptible to secondary nosocomial infections responsible for their death [12].…”