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.

Difference in virulence between Neisseria meningitidis serogroups W and Y in transgenic mice

“…The blood was then plated, and bacterial count was determined after overnight incubation at 37°C with 5% CO 2 . Cutaneous temperature was measured using an infrared thermometer (Bioseb) before infection and at 3 h and 24 h post-infection, and used to follow the clinical status of the mice during infection, as hypothermia has been reported as a sign of severe meningococcal infection in the mouse model [29]. Results were expressed as mean temperature loss in comparison with temperature before infection.…”

“…Post-infection with NmW and NmY isolates, blood was collected for analysis of cytokines. The proinflammatory cytokine CXCL1 was chosen as it has previously been shown to clearly and directly reflect the proinflammatory response in this model of systemic meningococcal infection [29]. It is expressed by inflammatory cells such as neutrophils and macrophages, and it has neutrophil chemotactic activity [30].…”

Use of Animal Models To Support Revising Meningococcal Breakpoints of β-Lactams

“…We have previously emphasized the advantages of in vivo bioluminescent imaging for real-time monitoring of meningococcal infections and their treatment (13,16). This technology is sensitive, rapid, and noninvasive.…”

Does Dexamethasone Helps in Meningococcal Sepsis?

“…Prompt recognition and aggressive early treatment are the only effective measures against IMD ( 3 ). Anti-inflammatory adjunctive treatment remains controversial and difficult to assess in patients, especially when it comes to septicaemia with or without meningitis caused by Neisseria meningitidis ( 4 ). Our earlier study showed that the use of dexamethasone has a limited effect on the outcome of the condition, primarily in re-establishing the functions of the blood–brain barrier in the cases of meningococcal sepsis with meningitis by normalizing the values of CSF sugar in comparison to cases in which no dexamethasone was used ( 5 ).…”