Genetic influence on cytokine production and fatal meningococcal disease

Lancet. 1997 Jan 18;349(9046):170-3. doi: 10.1016/s0140-6736(96)06413-6.


Background: To assess the genetic influence on cytokine production and its contribution to fatal outcome, we determined the capacity to produce tumour necrosis factor-alpha (TNF alpha) and interleukin-10 (IL-10) in families of patients who had had meningococcal disease.

Methods: We studied 190 first-degree relatives of 61 patients with meningococcal disease; we also studied 26 monozygotic twins. Production of cytokines was determined during endotoxin stimulation of whole-blood samples ex-vivo. Heritability was estimated in a pedigree-based maximum-likelihood model. DNA was typed for the G to A transition polymorphisms at position -308 and -238 in the TNF gene promoter.

Findings: Heritability in monozygotic twins was 0.60 for the production of TNF and 0.75 for the production of IL-10. Families with low TNF production had a tenfold increased risk for fatal outcome (OR 8.9, 95% CI 1.8-45), whereas high IL-10 production increased the risk 20-fold (19.5, 2.3-165). Families with both characteristics had the greatest risk. The transition polymorphisms in the TNF gene promoter were not associated with outcome.

Interpretation: Genetic factors substantially influence production of cytokines. An innate anti-inflammatory cytokine profile may contribute to fatal meningococcal disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Child
  • Child, Preschool
  • Diseases in Twins
  • Female
  • Humans
  • Infant
  • Interleukin-10 / biosynthesis*
  • Male
  • Meningitis, Meningococcal / genetics*
  • Meningitis, Meningococcal / immunology
  • Meningitis, Meningococcal / mortality
  • Mice
  • Middle Aged
  • Models, Genetic
  • Neisseria meningitidis / isolation & purification
  • Nuclear Family
  • Pedigree
  • Polymorphism, Genetic
  • Spouses
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Twins, Monozygotic


  • Tumor Necrosis Factor-alpha
  • Interleukin-10