gms | German Medical Science

Objectives: Trauma is still a leading cause of morbidity and mortality. These patients need a precise, early diagnostic to avoid complications like multiorgan failure or sepsis. The inflammation cytokines, commonly used for diagnostic, have short half-life that complicate their monitoring in serum/plasma and decrease their prognostic potential. In the present study we hypothesise that cytokines could be preserved from degradation in exosomes and therefore could be suggested as diagnostic and prognostic markers in polytrauma patients.

Methods: Plasma samples from polytraumatized patients (ISS 16, n=18) were collected at the emergency room (ER), 1 day, 2 days, 3 days and 5 days after trauma. Plasma-exosomes were isolated via size exclusion chromatography from polytraumatized patients as well as healthy volunteers (n=10). The systemic and exosomal concentrations of Interleukin (IL)-6, IL-10, IL-1β and TNF alpha were measured by using high-sensitive ELISAs. To investigate the diagnostic and prognostic potential of exosomal cytokines, data were correlated with clinical outcome parameters (injury severity, ventilation time, time on ICU, survival) documented in the electronical patients’ record.

Results: The isolated extracellular vesicles showed the typical size of exosomes (200 nm) and expressed exosome-specific tetraspanins CD9, CD8 and CD63. Despite the use of high-sensitive ELISAs, IL-1β and TNF alpha were not detected in exosomes. IL-6 and IL-10 were detectable in polytraumatized patient exosomes at all time points and the decrease with time of both, systemic and exosomal IL-6 concentrations, was found. Furthermore, the exosomal and systemic IL-6 concentrations correlated moderately (r² = 0.46). Exosomal IL-6 at ER correlated moderately with the Injury Severity Score (ISS, Mean 35.5 ± 11.5) (r²=0.46) and was associated with non-survival in polytrauma patients (p<0.05).In contrast to IL-6, no correlation between systemic and exosomal IL-10 concentrations was found. Exosomal IL-10 concentration remained the same amount throughout the observation time, whereas systemic IL-10 concentration was maximal in ER and was significantly reduced after 24 hrs.

Conclusion: The data of the present study support our hypothesis that some cytokines (IL-10, but not IL-6) are detectable in exosomes significantly longer as in plasma. This might indicate that they are protected from degradation. Although we did not find a correlation between IL-10 exosomal concentration and patient outcome, our data confirm that exosomal cytokines are of interest as potential diagnostic and prognostic markers in polytrauma patients and needs further detailed research.