title: CC-10004 but not thalidomide or lenalidomide inhibits lamina propria mononuclear cell TNF-α and MMP-3 production in patients with inflammatory bowel disease.
abstract: BACKGROUND
  Thalidomide, one of whose activities is to inhibit Tumour Necrosis Factor (TNF)-α production, has been reported to be an effective treatment for refractory inflammatory bowel disease (IBD). TNF-α driven production of matrix metalloproteinase (MMP)-3 by gut lamina propria mononuclear cells (LPMCs) is a major pathway of tissue injury in IBD; however the effect of thalidomide and newer more potent immunomodulatory derivatives on this pathway has not been studied.
  
  
  OBJECTIVE
  To investigate the effect of thalidomide, CC-4047 (pomalidomide), CC-5013 (lenalidomide), and CC-10004 (apremilast) on gut LPMC TNFα and MMP-3 production in patients with IBD.
  
  
  METHODS
  Gut LPMCs and myofibroblasts were isolated from patients with IBD, and cultured with thalidomide, CC-4047, CC-5013, and CC-10004. MMP-3 and TIMP-1 levels were determined by western blotting and real-time PCR, and TNF-α levels by ELISA.
  
  
  RESULTS
  CC-10004 significantly reduced both TNF-α production and MMP-3 production by cultured LPMCs. Thalidomide and CC-4047 and CC-5013 had no significant effect on the production of TNF-α or MMP-3 by LPMCs.
  
  
  CONCLUSIONS
  These results provides a mechanistic rationale for both the failure of lenalidomide (CC-5013) in a recent randomised controlled trial in Crohn's disease, and for the evaluation of CC-10004 as a novel oral therapy in the treatment of CD and UC.
authors.affiliation: Division of Infection, Inflammation and Repair, University of Southampton, School of Medicine, Southampton, UK; Department of Gastroenterology, Royal Hampshire County Hospital, Winchester, UK.
authors.forename: J N
authors.initials: JN
authors.lastname: Gordon
authors.forename: J D
authors.initials: JD
authors.lastname: Prothero
authors.forename: C A
authors.initials: CA
authors.lastname: Thornton
authors.forename: K M
authors.initials: KM
authors.lastname: Pickard
authors.forename: A
authors.initials: A
authors.lastname: Di Sabatino
authors.forename: P M
authors.initials: PM
authors.lastname: Goggin
authors.forename: S L
authors.initials: SL
authors.lastname: Pender
authors.forename: T T
authors.initials: TT
authors.lastname: Macdonald