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Endotoxin release and cytokine production in acute and chronic meningococcaemia
J M Prins1, F N Lauw, B H Derkx
1Department of Internal Medicine, Academic Medical Centre, Amsterdam, The Netherlands.
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.
Insights
Bacterial virulence factors may explain why chronic meningococcaemia is less severe. Isolates from severe septic shock released more endotoxin, while those from chronic cases induced lower IL-6 levels, suggesting diminished virulence in chronic meningococcaemia.
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Chronic meningococcaemia is a mild form of meningococcal disease.
- Bacterial virulence factors potentially influencing disease severity are not well understood.
Purpose of the Study:
- To compare the endotoxin-liberating ability and cytokine-inducing potential of Neisseria meningitidis isolates.
- To investigate if bacterial virulence factors correlate with disease severity in meningococcal disease.
Main Methods:
- Compared in vitro endotoxin release and cytokine induction (IL-6) of N. meningitidis isolates.
- Isolates were sourced from children with acute septic shock, chronic meningococcaemia, and asymptomatic carriers.
- Analyzed endotoxin and cytokine levels in patients with acute meningococcal septic shock.
Main Results:
- Isolates from septic shock patients released significantly higher median endotoxin levels in vitro compared to chronic or carrier isolates.
- Isolates from chronic meningococcaemia patients induced significantly lower median IL-6 levels ex vivo.
- No correlation was found between in vitro endotoxin release and in vivo patient endotoxin/cytokine levels in acute cases.
Conclusions:
- Results suggest diminished bacterial virulence in isolates causing chronic meningococcaemia.
- Factors beyond bacterial endotoxin-releasing potential contribute to the wide variation in patient responses during acute meningococcal septic shock.