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Inflamm Res. 2002 Nov;51(11):522-31.

RDP58, a locally active TNF inhibitor, is effective in the dextran sulphate mouse model of chronic colitis.

Author information

1
Division of Gastroenterology and Hepatology, Drexel University College of Medicine, 245 N 15th Street, Philadelphia, PA 19102-1192, USA, s.Murthy@drexel.edu

Abstract

OBJECTIVE AND DESIGN:

RDP58 is a novel anti-inflammatory peptide that inhibits TNF synthesis and upregulates heme oxygenase-1. RDP58 therapy was evaluated in the dextran sodium sulphate (DSS) model of chronic colitis.

MATERIAL:

Colitis was induced by giving DSS to mice (n = 8 animals/group). Toxicity studies were done in Rhesus monkeys (n = 5), dogs (n = 3) and mice (n = 10).

TREATMENT:

In colitis, mice were treated with p.o. vehicle (saline), RDP58 (5 and 10 mg/kg/day) or 5-ASA (50 mg/kg/day).

METHODS:

Disease activity index (DAI) was used as the endpoint of efficacy.

RESULTS:

RDP58 therapy significantly reduced DAI and histological scores in all animals. DAI scores in RDP58 treated animals declined faster than 5-ASA. RDP58 at 5 or 10 mg/ kg/day significantly reduced DAI compared to 5-ASA. RDP58 significantly reduced acute, chronic and total inflammation scores. It enhanced re-epithelialization by reducing crypt scores. RDP58 was not bioavailable and was well tolerated.

CONCLUSIONS:

Therapeutic efficacy of RDP58 combined with a lack of bioavailibility and toxicity suggest that RDP58 may be a promising new therapeutic for IBD.

PMID:
12540016
[Indexed for MEDLINE]
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