RDP58, a Novel Immunomodulatory Peptide with Anti-Inflammatory Effects. A Pharmacological Study in Trinitrobenzene Sulphonic Acid Colitis and Crohn Disease.

ABSTRACT

BACKGROUND: Tumour necrosis factor (TNF) plays a key role in the pathogenesis of Crohn disease (CD). RDP58 is a novel anti-inflammatory decapeptide which was developed using a novel rational design strategy. Recently, RDP58 has proved to be a potent inhibitor of TNF production at a post-transcriptional step. The aims of this study were to investigate the anti-inflammatory properties of RDP58 ex vivo in human CD and in vivo in an experimental model colitis. METHODS: Biopsies and lamina propria mononuclear cells from inflamed colonic mucosa of 18 CD patients were cultured for 24 h in the presence or absence of RDP58. TNF was quantified in a bioassay; interferon (IFN)-γ and interleukin (IL)-1ß levels were measured by enzyme-linked immunosorbent assays. Colitis was induced by intra-rectal administration of 2, 4, 6 trinitrobenzene sulphonic acid (TNBS) in rats. Inflammation was assessed following 7 days of oral therapy with RDP58 or vehicle alone. RESULTS: RDP58 led to decreased TNF and IFN-γ (but not IL-1ß) production by biopsies and lamina propria mononuclear cells from CD patients. In rats with TNBS-induced colitis, oral RDP58 therapy reduced weight loss and diarrhoea and improved macroscopic and histological inflammation scores. CONCLUSIONS: Our results suggest that RDP58 may be an effective therapy for CD with the clinical advantage of an oral administration.