Elevated nucleosome levels in systemic inflammation and sepsis.
OBJECTIVE
Multiple organ dysfunction syndrome is a frequent complication of severe sepsis and septic shock and has a high mortality. We hypothesized that extensive apoptosis of cells might constitute the cellular basis for this complication.


METHODS
Retrospective study.


METHODS
Medical and surgical wards or intensive care units of two university hospitals.


METHODS
Fourteen patients with fever, 15 with systemic inflammatory response syndrome, 32 with severe sepsis, and eight with septic shock.


METHODS
None.


RESULTS
We assessed circulating levels of nucleosomes, specific markers released by cells during the later stages of apoptosis, with a previously described enzyme-linked immunosorbent assay in these 69 patients with fever, systemic inflammatory response syndrome, severe sepsis, or septic shock. Severity of multiple organ dysfunction syndrome was assessed with sepsis scores, and clinical and laboratory variables. Elevated nucleosome levels were found in 64%, 60%, 94%, and 100% of patients with fever, systemic inflammatory response syndrome, severe sepsis, or septic shock, respectively. These levels were significantly higher in patients with septic shock as compared with patients with severe sepsis, systemic inflammatory response syndrome, or fever, and in nonsurvivors as compared with survivors. In patients with advanced multiple organ dysfunction syndrome, nucleosome levels correlated with cytokine plasma levels as well as with variables predictive for outcome.


CONCLUSIONS
Patients with severe sepsis and septic shock have elevated plasma levels of nucleosomes. We suggest that apoptosis, probably resulting from exposure of cells to excessive amounts of inflammatory mediators, might by involved in the pathogenesis of multiple organ dysfunction syndrome.
Zeerleder
Sacha
S
University Hospital, Bern, Switzerland.
Zwart
Bas
B
Wuillemin
Walter A
WA
Aarden
Lucien A
LA
Groeneveld
A B Johan
AB
Caliezi
Christoph
C
van Nieuwenhuijze
Annemarie E M
AE
van Mierlo
Gerard J
GJ
Eerenberg
Anke J M
AJ
Lämmle
Bernhard
B
Hack
C Erik
CE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology; D015415:Biomarkers / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood / Q000175:diagnosis* / Q000401:mortality; D009707:Nucleosomes / Q000378:metabolism*; D011237:Predictive Value of Tests; D011379:Prognosis; D012772:Shock, Septic / Q000097:blood / Q000175:diagnosis* / Q000401:mortality; D015996:Survival Rate; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000175:diagnosis* / Q000401:mortality
D015415:Biomarkers; D009707:Nucleosomes