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Orally administered RDP58 reduces the severity of dextran sodium sulphate induced colitis

¹ Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA
² SangStat, Fremont, California 94555, USA

Correspondence to:
Correspondence to:
Dr R Boismenu, Repligen Corporation, 41 Seyon Street, Building No 1, Suite 100, Waltham, MA 02453, USA;
rboismenu{at}repligen.com

ABSTRACT
Oral administration of the novel anti-inflammatory peptide RDP58 markedly reduced the severity of dextran sulphate sodium (DSS) colitis as determined by clinical and quantitative histological criteria. The architecture of the colonic epithelium in DSS treated mice receiving RDP58 remained relatively normal compared with that of control DSS treated animals. 5-Bromo-2'-deoxyuridine (BrdU) labelling studies showed a pronounced inhibition of colonic epithelial cell proliferation during DSS treatment, which was partially reversed by RDP58 therapy. Remarkably, RDP58 almost completely prevented colonic epithelial cell death induced by DSS treatment. RDP58 therapy also inhibited the accumulation of neutrophils in the colon of DSS treated mice and effectively down regulated tumour necrosis factor (TNF) expression. Preservation of the intestinal mucosa by RDP58 may thus derive from its influence on TNF expression as well as additional anti-inflammatory properties. These findings indicate that RDP58 represents a new, orally available agent potentially useful in the treatment of inflammatory bowel disease.

Keywords: rodents; inflammation; cytokines; mucosa

Abbreviations: BrdU, 5-bromo-2'-deoxyuridine; DSS, dextran sulphate sodium; ELISA, enzyme linked immunosorbent assay; HO-1, haem oxygenase-1; HTAB, hexadecyltrimethylammonium bromide; IBD, inflammatory bowel disease; IL, interleukin; INF, interferon ; mAb, monoclonal antibody; MPO, myeloperoxidase; RT-PCR, reverse transcriptase-polymerase chain reaction; TNF, tumour necrosis factor; TUNEL, Tdt mediated dUTP nick end labelling