The prognostic importance of interferon-γ-inducing factor (interleukin-18) during severe sepsis

Aim/Background: Interleukin-18 (IL-18), originally termed interferon (IFN)-gamma inducing factor, is a newly identified proinflammatory cytokine. As a first approach to the potential involvement of IL-18 in the pathogenesis of human sepsis, we studied its plasma concentrations in patients with severe sepsis. Methods: Plasma levels of IL-18 were determined in 20 consecutive patients with clinical diagnosis of sepsis. Severely injured patients (n = 30) with systemic inflammatory response syndrome, but without evidence of infection, and healthy volunteers (n = 30) were studied as control groups. To confirm the specific response of IL-18 to gram positive bacteria, heparinized whole blood from healthy volunteers was incubated with either lipopolysaccharide (LPS) or Staphylococcus aureus (SAC). Results: Median plasma concentrations of IL-18 were significantly increased in patients with gram-positive sepsis compared to patients with gram-negative infection, injured patients or healthy humans. Non-survivors and patients with septic shock revealed higher levels of IL-18 compared to survivors and septic patients without shock. While SAC markedly (p < 0.05) increased the release of IL-18 in whole blood, IFS was ineffective. Conclusion: These data provide evidence that IL-18 is predominantly produced during gram positive sepsis. Interleukin-18 may represent the first proinflammatory cytokine which differentiates between gram positive and gram negative sepsis. Thus, IL-18 is a useful tool in evaluating diagnosis and prognosis of gram positive sepsis.