The human response to infection is associated with distinct patterns of interleukin 23 and interleukin 27 expression

• Published in: Intensive care medicine 2008-04, Vol.34 (4), p.683-691
• Main Authors: O’Dwyer, Michael J., Mankan, Arun K., White, Mary, Lawless, Mathew W., Stordeur, Patrick, O’Connell, Brian, Kelleher, Dermot P., McManus, Ross, Ryan, Thomas
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anesthesiology; Bacteremia - immunology; Biological and medical sciences; Blood coagulation. Blood cells; Case-Control Studies; Critical Care Medicine; Disease Progression; Emergency Medicine; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; General aspects, investigation methods, hemostasis, fibrinolysis; Humans; Intensive; Intensive care medicine; Interferon-gamma - deficiency; Interferon-gamma - genetics; Interferon-gamma - immunology; Interleukin-17 - blood; Interleukin-17 - genetics; Interleukin-18 - blood; Interleukin-18 - genetics; Interleukin-23 - blood; Interleukin-23 - genetics; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Molecular and cellular biology; Original; Pain Medicine; Pediatrics; Pneumology/Respiratory System; Prospective Studies; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - blood; Survival Analysis; Systemic Inflammatory Response Syndrome - immunology
• ISSN: 0342-4642; 1432-1238
• DOI: 10.1007/s00134-007-0968-5

Objective The development and progression of severe sepsis is related to a deficiency in pro-inflammatory cytokine production, characterised by lesser IFNγ levels, which are not explained by variations in levels of the main putative regulator of IFNγ, namely IL-12. As alternative regulators of IFNγ 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. Design and setting A prospective observational trial in a mixed intensive care unit (ICU) and hospital wards in a university teaching hospital. Patients and participants Sixty-two ICU patients with severe sepsis, 13 bacteraemic patients with no acute critical illness, and 10 healthy controls. Measurements and 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 TNFα 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.