The human response to infection is associated with distinct patterns of interleukin 23 and interleukin 27 expression.
OBJECTIVE
The development and progression of severe sepsis is related to a deficiency in pro-inflammatory cytokine production, characterised by lesser IFNgamma levels, which are not explained by variations in levels of the main putative regulator of IFNgamma, namely IL-12. As alternative regulators of IFNgamma may be of greater importance in human sepsis, we investigated the hypothesis that the development of severe sepsis is related to variations in IL-18, IL-23 and IL-27 gene expression.


METHODS
A prospective observational trial in a mixed intensive care unit (ICU) and hospital wards in a university teaching hospital.


METHODS
Sixty-two ICU patients with severe sepsis, 13 bacteraemic patients with no acute critical illness, and 10 healthy controls.


RESULTS
All subjects were assayed for IL-18, IL-23 and IL-27 mRNA levels in peripheral blood. IL-27 mRNA levels distinguished between the three groups, with levels highest in the ICU group, intermediate in the bacteraemic group and lowest in the control group. IL-23 distinguished between the groups, with levels lowest in the ICU group. In late sepsis IL-23 and TNFalpha mRNA levels were directly related. IL-18 mRNA levels did not distinguish between the patient groups.


CONCLUSIONS
We conclude that the deficient pro-inflammatory response in patients with sepsis is expansive and includes deficient IL-23 and excessive IL-27 gene expression. This provides further evidence that upregulation of a cytokine-based immune response is beneficial in sepsis.
O'Dwyer
Michael J
MJ
Department of Anaesthesia, St James's Hospital, Dublin, Ireland.
Mankan
Arun K
AK
White
Mary
M
Lawless
Mathew W
MW
Stordeur
Patrick
P
O'Connell
Brian
B
Kelleher
Dermot P
DP
McManus
Ross
R
Ryan
Thomas
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016470:Bacteremia / Q000276:immunology; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D020381:Interleukin-17 / Q000097:blood* / Q000235:genetics; D020382:Interleukin-18 / Q000097:blood* / Q000235:genetics; D053759:Interleukin-23 / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012333:RNA, Messenger / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology*
D020381:Interleukin-17; D020382:Interleukin-18; D053759:Interleukin-23; D012333:RNA, Messenger; D007371:Interferon-gamma