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)-gamma and interleukin (IL)-1beta 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-gamma (but not IL-1beta) 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.

• Authors: A Bourreille, M Doubremelle, D Raingeard de la Blétière, J P Segain, C Toquet, R Buelow, J P Galmiche
• Journal: Scandinavian journal of gastroenterology (Scand J Gastroenterol) Vol. 38 Issue 5 Pg. 526-32 (May 2003) ISSN: 0036-5521 [Print] England
• PMID: 12795464 (Publication Type: Clinical Trial, Evaluation Study, Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Histocompatibility Antigens Class I
• Interleukin-1
• Peptides
• Tumor Necrosis Factor-alpha
• allotrap
• Interferon-gamma
• Trinitrobenzenesulfonic Acid

Topics

• Adolescent
• Adult
• Aged
• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Colitis (chemically induced, immunology)
• Crohn Disease (drug therapy, immunology)
• Female
• Histocompatibility Antigens Class I (pharmacology, therapeutic use)
• Humans
• Interferon-gamma (biosynthesis, immunology)
• Interleukin-1 (biosynthesis, immunology)
• Intestinal Mucosa (drug effects)
• Male
• Middle Aged
• Models, Animal
• Peptides (pharmacology, therapeutic use)
• Prospective Studies
• Rats
• Rats, Sprague-Dawley
• Trinitrobenzenesulfonic Acid
• Tumor Necrosis Factor-alpha (biosynthesis, immunology)