Microvesicles are cell
-derived signaling particles emerging as important mediators and
biomarkers of systemic inflammation, but their production in severe burn injury patients has
not been described. In this pilot investigation, we measured circulating microvesicle levels
following severe burns, with severe sepsis patients as a comparator group.
We hypothesized
that levels of circulati
ng vascular cell
-derived microvesicles are elevated acutely following
burns injury, mirroring clinical severity due to the early onset and prevalence of systemic
inflammatory response syndrome (SIRS) in these patients. Blood samples were obtained
from pat
ients with moderate to severe thermal
injury burns, with severe sepsis, and from
healthy volunteers. Circulating microvesicles derived from total leukocytes, granulocytes,
monocytes, and endothelial cells were quantified in plasma by flow cytometry.
All
circulating microvesicle subpopulations were elevated in burns
patients on day of admission
(day 0) compared to healthy volunteers (leukocyte
-microvesicles: 3.5
-fold,
p
=0.005;
granulocyte
-microvesicles: 12.8-
fold, p<
0.0001; monocyte
-microvesicles: 20.4
-fold,
p<0.0001; endothelial
- microvesicles: 9.6
-fold,
p
=0.01), but decreased significantly by day 2.
Microvesicle levels were increased with severe sepsis, but less consistently between patients.
Leukocyte
- and granulocyte
-derived microvesicles on day 0 correlated with clinical
assessment scores and were higher in burns ICU non-
survivors compared to survivors
(leukocyte MVs 4.6 fold,
p
=0.002; granulocyte MVs 4.8 fold,
p
=0.003). Mortality prediction
analysis of area und
er receiver operating characteristic curve was 0.92 (
p
=0.01) for total
leukocyte microvesicles and 0.85 (
p
=0.04) for granulocyte microvesicles. These findings
demonstrate, for the first time, acute increases in circulating microvesicles following burns
inj
ury in patients and point to their potential role in propagation of sterile SIRS
-related
pathophysiology.