Synergistic effects of systemic trefoil factor family 1 (TFF1) peptide and epidermal growth factor in a rat model of colitis.
Novel therapies for the treatment of colitis are required. We therefore examined the potential value of the trefoil factor family 1 (TFF1) peptide and epidermal growth factor (EGF) alone and in combination. Effects of TFF1- Cys58 +/- EGF on an in vitro HT29 cell wounding model of restitution showed synergistic activity when used in combination. In addition, animals had colitis induced by adding 4% dextran sulphate sodium (DSS) to the drinking water for 7 days and they also received twice daily subcutaneous injections of test peptides. Treatment with TFF1-Cys58 alone (100 microg/kg) reduced histological colitis score by 22%, but the TFF1-Ser58 variant was ineffective. In a second study, TFF1-Cys58 reduced histological colitis score by 15%, EGF (600 microg/kg) by 26%, and an additive response (42% reduction) was demonstrated when used together (P < 0.01 versus either peptide given alone). Similar results were found using tissue myeloperoxidase (MPO) activity as a marker of inflammation. Where clinical risk/benefit seems justified, these initial studies suggest that combination therapy of systemic EGF and TFF peptides may prove useful for treatment of colitis in patients with disease extending beyond the reach of topical (enema) therapy.
FitzGerald
A J
AJ
Department of Gastroenterology, Imperial College Faculty of Medicine, Hammersmith Hospital, Ducane Road, London W12 0NN, UK. r.playford@imperial.ac.uk
Pu
M
M
Marchbank
T
T
Westley
B R
BR
May
F E B
FE
Boyle
J
J
Yadollahi-Farsani
M
M
Ghosh
S
S
Playford
R J
RJ
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000473:pathology*; D016264:Dextran Sulfate / Q000633:toxicity; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D008070:Lipopolysaccharides; D008297:Male; D009077:Mucins; D009124:Muscle Proteins; D010455:Peptides; D009195:Peroxidase / Q000378:metabolism; D011506:Proteins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D000071163:Trefoil Factor-1; D000071164:Trefoil Factor-2; D025521:Tumor Suppressor Proteins; D014945:Wound Healing / Q000187:drug effects*
D008070:Lipopolysaccharides; D009077:Mucins; D009124:Muscle Proteins; D010455:Peptides; D011506:Proteins; D011994:Recombinant Proteins; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1; D000071164:Trefoil Factor-2; D025521:Tumor Suppressor Proteins; D004815:Epidermal Growth Factor; D016264:Dextran Sulfate; D009195:Peroxidase