Attenuation of monocyte proinflammatory cytokine responses to Neisseria meningitidis in children by erythropoietin.
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.
Schultz
C
C
Department of Paediatrics, Medical University of Lübeck, Germany. schultz@paedia.ukl.mu-luebeck.de
Zimmer
J
J
Härtel
C
C
Rupp
J
J
Temming
P
P
Strunk
T
T
D000328:Adult; D000367:Age Factors; D002478:Cells, Cultured; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis*; D004921:Erythropoietin / Q000276:immunology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015850:Interleukin-6 / Q000096:biosynthesis; D008589:Meningococcal Infections / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D009345:Neisseria meningitidis / Q000145:classification / Q000276:immunology*; D011994:Recombinant Proteins; D012703:Serotyping; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin
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