Functional immune monitoring in severely injured patients—A pilot study

Abstract

After severe trauma, the resulting excessive inflammatory response is countered by compensatory anti‐inflammatory mechanisms. The systemic inflammatory response to trauma enhanced by inappropriately timed surgical second hits may be detrimental for the patient. On the other hand, overwhelming anti‐inflammatory mechanisms may put patients at increased risk from secondary local and systemic infections. The ensuing sepsis and organ dysfunction due to immune dysregulation remain the leading causes of death after injury. To date, there are no clinically applicable techniques to monitor the pro‐/anti‐inflammatory immune status of the patients and the remaining ability to react to microbial stimuli. Therefore, in the present study, we used a highly standardized and easy‐to‐use system to draw peripheral whole blood from polytraumatized patients (ISS ≥ 32, n = 7) and to challenge it with bacterial lipopolysaccharide. Secreted cytokines were compared with those in samples from healthy volunteers. We observed a significant decrease in the release of monocyte‐derived mediators. Surprisingly, we detected stable or even increased concentrations of cytokines related to T cell maturation and function. For clinical practicability, we reduced the incubation time before supernatants were collected. Even after an abbreviated stimulation period, a stable release of almost all analysed parameters in patient blood could be detected. In conclusion, the data are indicative of a clinically well‐applicable approach to monitor the immune status in severely injured patients in a short time. This may be used to optimize the timing of necessary surgical interventions to avoid a boost of proinflammation and reduce risk of secondary infections.

Animal-Free Human Whole Blood Sepsis Model to Study Changes in Innate Immunity

“…To prevent stimulation after venipuncture ex vivo, a variety of models have been previously proposed of whole blood being supplemented with an anticoagulant and/or being encased in a specially coated system. Human whole blood models of coated circuits or whole blood cultures in combination with defined anticoagulation, for example, heparin or hirudin, have been widely used and characterized in recent years (12)(13)(14)(15)(16)(17)(18). In general, these models address a specific focus and produced the respective specific answers.…”

“…For example, global blood parameters (e.g. pH and glucose concentration) have frequently not been reported, making it difficult to interpret the presented data and to transfer them into the physiological in vivo context of the human body ( 12 – 14 , 16 , 18 – 21 ). There is also a concomitant research gap with regards to a comprehensive study of blood physiology ex vivo while synchronically assessing important immunological functions and activation markers.…”

Impact of surface coating and systemic anticoagulants on hemostasis and inflammation in a human whole blood model

“…Therefore, an increased response of thrombocytes after stimulation with ADP could be observed in citrated blood compared to other anticoagulants like heparin, hirudin and enoxaparin [ 44 ]. Scientific models for incubating human whole blood ex vivo to address immunological and pharmacotherapeutic questions have been applied successfully [ 29 , 45 – 47 ]. However, these models have limitations in investigating coagulation physiology, as they relied on substantial anticoagulation.…”

Cytological Effects of Serum Isolated from Polytraumatized Patients on Human Bone Marrow-Derived Mesenchymal Stem Cells

“…In the subsequent D5 and D10 groups, proinflammatory and anti-inflammatory factors are in a relatively balanced state, as their concentrations are comparable to the HS group and showed a fluctuation trend after trauma to maintain a long-term balance which is in line with the theory of SIRS/CARS balancing, as well as the latest PICS theory [ 50 ]. A comparable study was carried out by Halbgebauer et al [ 51 ] which conducted a cytokine analysis from seven polytrauma patients (ISS ≥ 32, six males and one female) four hours and one and five days posttrauma and treated the whole blood with or without lipopolysaccharide (LPS). In the results of Halbgebauer et al, the proinflammatory factors IL-12 and IFN- γ were downregulated after trauma in D1 when compared with the healthy group, and an upward trend was discovered from D1 to D10.…”