A peptide sequence from platelet factor 4 (CT-112) is effective in the treatment of type II collagen induced arthritis in mice.
OBJECTIVE
Platelet factor 4 (PF-4) is a critical alpha chemokine in inflammation and injury responses, with multiple effects upon cellular activities. Discrete peptide sequences of the PF-4 molecule have been shown to retain biological activity. Our aim was to examine the influence of the PF-4 derived octapeptide (CT-112; TTSQVRPR) on type II collagen induced arthritis in mice, to determine if this peptide exhibited antiinflammatory properties.


METHODS
DBA/1 mice were treated with CT-112 from either the time of immunization with type II collagen or from the initial onset of arthritis.


RESULTS
CT-112 both prevented the development of arthritis in mice treated prophylactically and reduced progression of disease in animals treated therapeutically, and was active when delivered by either subcutaneous injection or oral gavage. No marked immunosuppressive effects were observed during CT-112 treatment, with only moderate decrease in antibody levels and mitogen responses. A significant reduction of the circulating levels of IL-1 was a consistent finding in mice treated therapeutically with CT-112.


CONCLUSIONS
These data suggest PF-4 derived octapeptide exerts antiinflammatory effects of experimental arthritis in mice.
Wooley
P H
PH
Division of Rheumatology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Schaefer
C
C
Whalen
J D
JD
Dutcher
J A
JA
Counts
D F
DF
D000284:Administration, Oral; D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D016918:Arthritis, Reactive / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003094:Collagen / Q000276:immunology / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008811:Mice, Inbred DBA; D008934:Mitogens / Q000494:pharmacology; D010446:Peptide Fragments / Q000032:analysis*; D010978:Platelet Factor 4 / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology; D013778:Tetrazolium Salts; D013844:Thiazoles / Q000276:immunology; D045162:Thiazolidinediones
D016207:Cytokines; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D008934:Mitogens; D010446:Peptide Fragments; D013778:Tetrazolium Salts; D013844:Thiazoles; D045162:Thiazolidinediones; D003208:Concanavalin A; D010978:Platelet Factor 4; C051003:risarestat; D003094:Collagen