A predominantly anti-inflammatory cytokine profile is associated with disease severity in meningococcal sepsis

Objective: This study aimed to determine whether an anti-inflammatory profile in meningococcal disease is associated with an increased risk of severe disease or septic shock. Design and setting: Prospective observational study in a tertiary care children's hospital. Patients and participants: 63 children with confirmed meningococcal disease. Interventions: Plasma concentrations of interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF) were assayed on admission. Receiver operator characteristic curve analysis was used to determine optimum thresholds for IL-1Ra: TNF, IL-1Ra: IL-6 and IL-1Ra: IL-8 ratios. Measurements and results: Median IL-1Ra: TNF and IL-1Ra: IL-6 ratios were significantly higher in severe disease with septic shock than in severe disease without septic shock and in non severe disease (IL-1Ra: TNF 263 vs. 185 vs. 108; IL-1Ra: IL-6 139 vs. 23 vs. 17). Median IL-1Ra: IL-8 ratios were not significantly different in the three groups. A significantly larger proportion of children with high IL-1Ra: TNF-alpha and IL-1Ra: IL-6 ratios developed severe disease with septic shock than those with a low ratios (95.2% vs. 4.8%; 76.2% vs. 23.8%). Conclusions: An anti-inflammatory profile appears to be associated with the development of severe disease and septic shock in meningococcal sepsis. This may imply that experimental new therapies of pro-inflammatory cytokine inhibition and anti-inflammatory cytokines in meningococcal disease could be detrimental.