Attenuation of monocyte proinflammatory cytokine responses to Neisseria meningitidis in children by erythropoietin

Clin Exp Immunol. 2008 Nov;154(2):187-91. doi: 10.1111/j.1365-2249.2008.03760.x. Epub 2008 Sep 8.

Abstract

Meningococcal disease is a leading infectious cause of death in children in industrialized countries. The induction of high levels of proinflammatory cytokines has been implicated in the pathogenesis of Neisseria meningitidis-related multi-organ failure. Here, we demonstrate that N. meningitidis serotypes A and B induce significantly higher levels of tumour necrosis factor (TNF)-alpha positive cells in vitro in infants and young children compared with adults (serotype A/B; infants: 64.9%/63.9%; children: 77.8%/64.3% versus adults: 27.7%/32%; P < 0.005). Serotype A induces also higher levels of interleukin (IL)-6 positive cells in neonates and infants compared with adults (serotype A; newborn 55.4%; infants 58.8% versus adults 49%; P < 0.05). Treatment with human recombinant erythropoietin in vitro resulted in significant attenuation of the N. meningitidis-induced proinflammatory response in all age groups (reduction rate of erythropoietin for IL-6 after stimulation with serotype B: newborn 28%, infants 15%, children 23% and adults 28% and for TNF-alpha after stimulation with serotype B: newborn 27%, infants 22%, children 20% and adults 28%; P < 0.05). We conclude that (i) Neisseria meningitidis induces a higher TNF-alpha response in infants and children compared with adults and (ii) erythropoietin was able to attenuate IL-6 and TNF-alpha production in all investigated age groups. These data may explain the high incidence of meningococcal infection in infants and makes erythropoietin a potentially attractive candidate for interventional strategies in an otherwise devastating course of the disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Cells, Cultured
  • Child, Preschool
  • Cytokines / biosynthesis*
  • Erythropoietin / immunology*
  • Humans
  • Infant
  • Infant, Newborn
  • Interleukin-6 / biosynthesis
  • Meningococcal Infections / immunology*
  • Monocytes / immunology*
  • Neisseria meningitidis / classification
  • Neisseria meningitidis / immunology*
  • Recombinant Proteins
  • Serotyping
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Cytokines
  • Interleukin-6
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Erythropoietin