Endotoxin release and cytokine production in acute and chronic meningococcaemia

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 meninigitidis 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.

Association of chronic meningococcemia with infection by meningococci with underacylated lipopolysaccharide

“…12 In this study meningococcal isolates were also derived from the Netherlands Reference Laboratory for Bacterial Meningitis. The nine strains from chronic meningococcemia patients were also included in the current study.…”

“…Also, the median endotoxin-liberating ability was shown to be significantly lower in the strains from chronic meningococcemia patients than those from both other categories. 12 The authors concluded that clinical severity of disease could be explained by differences in LPS immunotype of N. meningitidis strains or differences in shedding of bacterial membranes. Our results show that differences in LPS structure caused by lpxL1 mutations account for the low grade infection in 48% of chronic meningococcemia cases.…”

Update on Meningococcal Disease with Emphasis on Pathogenesis and Clinical Management

“…During invasive disease, these structures can be visualized in plasma or cerebrospinal fluid (CSF) by electron microscopy (48, 445). Strains isolated from patients with meningococcal septic shock liberate more endotoxin than do strains isolated from patients with chronic benign meningococcemia (368).…”

Endotoxin: The uninvited guest

“…In one study, the median of endotoxin concentration in plasma for septic patients has been reported to be around 2.5 EU/mL (ranging from nondetectable levels to 12 EU/mL) [19]. In children affected by meningococcaemia and admitted for septic shock, the levels were 5 EU/ mL (range nondetectable to 40 EU/mL) [20].…”