Endotoxin release and cytokine production in acute and chronic meningococcaemia

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Abstract
Chronic meningococcaemia is a relatively benign manifestation of meningococcal disease. Whether bacterial virulence factors are responsible for this benign course has not been studied. We compared the in vitro endotoxin-liberating ability and cytokine-inducing potential of 31 Neisseria meningitidis isolates obtained from children with acute septic shock with that of nine isolates obtained from patients with chronic meningococcaemia and 12 isolates obtained from carriers with respiratory symptoms. The median endotoxin level released in vitro after 3 h of incubation was significantly higher for isolates causing septic shock compared with isolates from the other two groups (P = 0.01 and 0.02, Mann–Whitney test). This was not explained by differences in bacterial growth rate in vitro. The median IL-6 levels in whole blood ex vivo after 4 h of incubation were also significantly lower for isolates causing chronic meningococcaemia (P = 0.04, Mann–Whitney test). The endotoxin and cytokine levels measured on admission in the 31 children with acute meningococcal septic shock showed a 1000-fold variation. No relationship was established between the amount of endotoxin released by the causative microorganisms in vitro and the endotoxin or cytokine levels in the corresponding 31 children. These results suggest a diminished bacterial virulence for isolates causing chronic meningococcaemia. However, other factors than the endotoxin-releasing potential of the microorganism involved are responsible for the wide variation in endotoxin and therefore cytokine levels in patients with acute meningococcal septic shock.