ABSTRACT
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. 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 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.
