A Peptide Sequence From Platelet Factor 4 (CT-112) Is Effective in the Treatment of Type II Collagen Induced Arthritis in Mice

J Rheumatol. 1997 May;24(5):890-8.

Abstract

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.

Conclusion: These data suggest PF-4 derived octapeptide exerts antiinflammatory effects of experimental arthritis in mice.

MeSH terms

  • Administration, Oral
  • Amino Acid Sequence
  • Animals
  • Antibody Specificity
  • Arthritis, Reactive / chemically induced
  • Arthritis, Reactive / drug therapy*
  • Arthritis, Reactive / prevention & control
  • Cell Division / drug effects
  • Cell Division / immunology
  • Cells, Cultured
  • Collagen* / immunology
  • Collagen* / pharmacology
  • Concanavalin A / pharmacology
  • Cytokines / blood
  • Disease Models, Animal
  • Enzyme Inhibitors / immunology
  • Lipopolysaccharides / pharmacology
  • Mice
  • Mice, Inbred DBA
  • Mitogens / pharmacology
  • Peptide Fragments / analysis*
  • Platelet Factor 4 / chemistry*
  • Platelet Factor 4 / immunology
  • Platelet Factor 4 / pharmacology*
  • Spleen / cytology
  • Tetrazolium Salts
  • Thiazoles / immunology
  • Thiazolidinediones*

Substances

  • Cytokines
  • Enzyme Inhibitors
  • Lipopolysaccharides
  • Mitogens
  • Peptide Fragments
  • Tetrazolium Salts
  • Thiazoles
  • Thiazolidinediones
  • Concanavalin A
  • Platelet Factor 4
  • risarestat
  • Collagen