title: Evaluation of Anti-inflammatory Effects of Steroids and Arthritis-Related Biotherapies in anIn VitroCoculture Model with Immune Cells and Synoviocytes.
abstract: BACKGROUND
  During rheumatoid arthritis (RA), steroids and biotherapies are used alone and combined. Efficacy has been established in clinical trials but their differential effects at the cellular level are less documented. The aim was to study these cellular effects using anin vitromodel with synoviocytes interacting with peripheral blood mononuclear cells (PBMC) to reproduce the interactions in the RA synovium.
  
  
  METHODS
  Activated-PBMC were cocultured with RA synoviocytes during 48 h. A dose-response of methylprednisolone (MP) was tested and different biotherapies (Infliximab, Etanercept, Adalimumab, Tocilizumab, Abatacept, and Rituximab) were added alone or in combination with MP. Cytokine production (IL-17, IL-6, IL-1β, IFN-γ and IL-10) was measured by ELISA.
  
  
  RESULTS
  Addition of MP to cocultures inhibited the production of all cytokines. The response to the biotherapies alone was treatment-dependent. IL-17 production was inhibited only by Tocilizumab (p= 0.004), while IL-6 was decreased only by Infliximab (p≤ 0.002). IL-1β level was affected in all conditions (p≤ 0.03). IFN-γ production was mainly decreased by Infliximab (p= 0.004) and IL-10 by Infliximab and Tocilizumab (p≤ 0.004). The combination MP and biotherapies did not induce an additional effect on pro-inflammatory cytokine inhibition. The combination MP and biotherapies induced a higher IL-10 secretion than MP alone, mainly with Rituximab.
  
  
  CONCLUSIONS
  Steroids inhibited the secretion of all cytokines, and low doses were as potent. The anti-inflammatory effect of biotherapies was dependent on their mechanism of action. MP and biotherapy combination did not enhance the inhibitory effect on pro-inflammatory cytokines but could have a beneficial effect by increasing IL-10 production.
authors.affiliation: Immunogenomics and Inflammation Research Unit, EA 4130, Edouard Herriot Hospital, Hospices Civils de Lyon and University Claude Bernard Lyon 1 , Lyon , France.
authors.forename: Mélissa
authors.initials: M
authors.lastname: Noack
authors.affiliation: Immunogenomics and Inflammation Research Unit, EA 4130, Edouard Herriot Hospital, Hospices Civils de Lyon and University Claude Bernard Lyon 1 , Lyon , France.
authors.forename: Ndiémé
authors.initials: N
authors.lastname: Ndongo-Thiam
authors.affiliation: Immunogenomics and Inflammation Research Unit, EA 4130, Edouard Herriot Hospital, Hospices Civils de Lyon and University Claude Bernard Lyon 1 , Lyon , France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Miossec
keywords: biotherapies; cell interaction; methylprednisolone; pro-inflammatory cytokines; rheumatoid arthritis