Anti-inflammatory cytokine response and the development of multiple organ failure in severe sepsis.
BACKGROUND
The production of proinflammatory cytokines activates the systemic inflammatory response in sepsis. Patients also develop a compensatory anti-inflammatory reaction, which may have an important down-regulatory effect on the overactive inflammation. However, the role of this anti-inflammatory response in sepsis is not completely clarified. In this prospective study, we investigated the relationship between the pro- and anti-inflammatory cytokine profiles in severe sepsis and their role in the development of multiple organ failure (MOF).


METHODS
Thirty-eight patients meeting the criteria for severe sepsis were studied. MOF was defined as a maximum SOFA score of 10 or higher. Serial measurements of the proinflammatory IL-6 and IL-1beta and the anti-inflammatory IL-10 and IL-1ra were used. The cytokine samples were taken at the onset of sepsis and on the third and fifth day during the ICU period.


RESULTS
The initial IL-10 and IL-1ra responses were identical in patients with or without MOF. The anti-inflammatory cytokine levels remained elevated in the MOF patients, whereas in patients without MOF the levels declined. The IL-6/IL-10 ratio was significantly higher in the MOF patients on days 1 and 3 compared with patients without MOF.


CONCLUSIONS
We could not demonstrate overproduction of anti-inflammatory IL-10 in MOF patients. On the contrary, the high IL-6/IL-10 ratio indicates that IL-10 deficiency may contribute to the development of MOF in severe sepsis.
Loisa
P
P
Departments of Anaesthesia and Intensive Care, Tampere University Hospital, Tampere, Finland. pekka.loisa@phks.fi
Rinne
T
T
Laine
S
S
Hurme
M
M
Kaukinen
S
S
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology; D010100:Oxygen / Q000097:blood; D011446:Prospective Studies; D018805:Sepsis / Q000378:metabolism* / Q000382:microbiology / Q000503:physiopathology; D014655:Vascular Resistance / Q000187:drug effects
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016753:Interleukin-10; D010100:Oxygen