title: Impact of corticosteroids on experimental meningococcal sepsis in mice.
abstract: Neisseria meningitidis is responsible for septicemia and meningitis with high fatality that is associated with an excessive inflammatory reaction particularly with hyperinvasive isolates of the clonal complex ST-11 (cc11). However, anti-inflammatory adjuvant treatment remains controversial and difficult to assess in patients. We addressed this topic in a well-defined experimental meningococcal infection in transgenic mice expressing the human transferrin. Mice were infected by intra-peritoneal challenge with bioluminescent serogroup C/cc11 strain. After 3h of infection mice were differentially treated every 6h by saline, amoxicillin alone or amoxicillin and dexamethasone (DXM). Infected mice were scored for clinical status, temperature and weight. Biological markers of inflammation were also quantified. Significant clinical improvement was observed in mice treated with amoxicillin and DXM compared to the two other groups. A significant reduction of the inflammatory reaction assessed by CRP and Lipocalin 2 (two acute phase proteins) was also observed with this treatment. DXM significantly increased blood levels of IL-10 at 6h post-infection. DXM/amoxicillin treated mice, compared to the two other groups, also showed lower levels of TNF-α and lower bacterial blood load assessed by serial dilutions of blood and bioluminescence dynamic imaging. Our results suggest that DXM, added to an appropriate antibiotic therapy, has a beneficial effect on experimental sepsis with a hyperinvasive meningococcal strain in transgenic mice expressing human transferrin. This is most likely due to the reduction of inflammatory response by an early induction of IL-10 cytokine. These data may allow better decision-making to use or not corticotherapy during meningococcal sepsis.
authors.affiliation: Institut Pasteur, Unité des Infections Bactériennes Invasives, 28 rue du Dr Roux, 75724 Paris Cedex 15, France; Institut Pasteur, Université Paris Descartes, Sorbonne Paris, Cité, France.
authors.forename: Michaël
authors.initials: M
authors.lastname: Levy
authors.affiliation: Institut Pasteur, Unité des Infections Bactériennes Invasives, 28 rue du Dr Roux, 75724 Paris Cedex 15, France; Institut Pasteur, Université Paris Descartes, Sorbonne Paris, Cité, France.
authors.forename: Ana
authors.initials: A
authors.lastname: Antunes
authors.affiliation: Institut Pasteur, Unité Histopathologie Humaine et Modèles Animaux, 28 rue du Dr Roux, 75724 Paris Cedex 15, France; Institut Pasteur, Université Paris Descartes, Sorbonne Paris, Cité, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Fiette
authors.affiliation: Institut Pasteur, Unité des Infections Bactériennes Invasives, 28 rue du Dr Roux, 75724 Paris Cedex 15, France; Institut Pasteur, Université Paris Descartes, Sorbonne Paris, Cité, France.
authors.forename: Ala-Eddine
authors.initials: AE
authors.lastname: Deghmane
authors.affiliation: Institut Pasteur, Unité des Infections Bactériennes Invasives, 28 rue du Dr Roux, 75724 Paris Cedex 15, France; Institut Pasteur, Université Paris Descartes, Sorbonne Paris, Cité, France. Electronic address: mktaha@pasteur.fr.
authors.forename: Muhamed-Kheir
authors.initials: MK
authors.lastname: Taha
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology* / Q000627:therapeutic use; D000658:Amoxicillin / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004347:Drug Interactions; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005838:Genotype; D006801:Humans; D008589:Meningococcal Infections / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009345:Neisseria meningitidis / Q000235:genetics / Q000502:physiology*; D018805:Sepsis / Q000150:complications*; D014168:Transferrin / Q000235:genetics
chemical_list: D000305:Adrenal Cortex Hormones; D015415:Biomarkers; D016207:Cytokines; D014168:Transferrin; D003907:Dexamethasone; D000658:Amoxicillin
keywords: Corticosteroids; Cytokine; Inflammation; Meningococcus; Mice; Sepsis