Background: Immune response to sepsis is complex. Several alterations of the innate response have been described and some even observed in other severe injuries. However, the comprehensive description of immune alterations developing over time in a large cohort of patients has never been done so far. In addition, it is not known whether these alterations depend on the type of injury (infectious vs sterile) and if they are associated with an increased risk of deleterious outcomes.
Materials/methods: A prospective longitudinal observational study was set up in Edouard Herriot Hospital (Lyon-France, December 2015 – March 2018). A total of 354 ICU patients suffering from sepsis, severe trauma or after major surgery, and 175 healthy volunteers were enrolled. Blood specimens were collected once from volunteers and three times from patients during the first week of ICU stay. Systemic inflammation was monitored by measuring IL-6 and IL-10 plasma concentrations. The innate response was measured by assessing cell numbers, phenotypes (immature neutrophils, MHC class II expression on monocytes), functions (cytokine production), and mRNA levels (S100A9, CD74, CX3CR1) with standardized tests.
Results: Injury-induced innate immune profile was similar in the 3 groups of patients and characterized by a major rise of circulating immature neutrophils in number and proportion whereas the number of circulating monocytes was not modified. However, starting from D1 after injury, monocytes were characterized by a major decrease in MHC class II expression correlated with altered TNFalpha production to LPS ex vivo. Intensity of these injury-induced alterations was maximal at D1, inversely correlated with systemic pro and anti-inflammatory responses and decreased overtime. The persistence at the end of the first week after injury of profound monocyte alterations was associated with an increased risk of death and secondary infections.
Conclusions: Our results show the complexity and evolution of the innate immune response after injury. This response combines an initial physiologic stress immune response with the concomitant development of monocyte alterations. When persisting, these alterations are associated with deleterious outcomes in accordance with the development of delayed injury-acquired immunodeficiency. Our data support the rationale for an immune intervention to restore functional immune response in these patients.