Analysis of the impact of corticosteroids adjuvant treatment during experimental invasive meningococcal infection in mice

Publication date: August 2018Source: Steroids, Volume 136Author(s): Michaël Levy, Ala-Eddine Deghmane, Myriam Aouiti-Trabelsi, Stéphane Dauger, Albert Faye, Patricia Mariani-Kurkdjian, Muhamed-Kheir TahaAbstractInvasive meningococcal disease (IMD) is usually associated with intense inflammatory response that is correlated with severe infection. Corticosteroids may regulate this inflammatory response through an early but transient induction of IL-10 that is suggested to improve the outcome of IMD. We explored the mechanism of action of corticosteroids as an adjuvant treatment to antibiotics. Transgenic mice expressing the human transferrin were infected by a hyperinvasive meningococcal strain and transcriptomic analysis were then performed in the blood for all conditions of infection and treatment. Infected untreated mice, infected antibiotic-treated mice and infected amoxicillin and dexamethasone-treated mice were compared. Treatment using both corticosteroids and antibiotics was associated with differential gene expression in the blood especially in Monocytes-Macrophages pathways. Depletion of these cells in infected mice was associated with a more severe bacterial infection and uncontrolled production of both pro-inflammatory and anti-inflammatory cytokines. Accordingly, children suffering from severe IMD had low counts of monocytes at admission. Our data are in favor of a role of corticosteroids in enhancing a polarization from pro-inflammatory to anti-inflammatory pheno...

Source: Steroids - July 10, 2018 Category: Drugs & Pharmacology Source Type: research