Derivatives of human beta-casein fragments (54-59) exhibit highly potent immunosuppressant activity

Int Immunopharmacol. 2009 Aug;9(9):1092-6. doi: 10.1016/j.intimp.2009.05.005. Epub 2009 May 20.

Abstract

Human beta-casein fragment (54-59) having the amino acid sequence Val-Glu-Pro-Ile-Pro-Tyr, has shown potent immunostimulant activity. Several analogs of this hexapeptide have been synthesized with modification at the N-terminal region and two analogs, viz. peptide I and peptide II have shown significant immunosuppressant activity in-vivo mouse model. Effect on cell mediated immunity (CMI) and humoral immunity was studied in mouse/SRBC model. Both the peptides failed to stimulate immune response in vivo and showed inhibition of CMI and humoral response to sheep red blood cells (SRBC). Peptides showed inhibition in alloantigen induced lymphocyte proliferation, i.e., mixed lymphocyte reaction (MLR) in vitro. Treatment with peptides inhibited the production of interferon-gamma (IFN-gamma), and increased the production of interleukin-4 (IL-4) as well as improved the skin graft survival. Cyclosporine a known immunosuppressant showed similar effect on mouse model. Present study thus provides a lead for the development of safe and effective immunosuppressant.

MeSH terms

  • Administration, Oral
  • Amino Acid Substitution
  • Animals
  • Caseins / chemistry
  • Cell Proliferation / drug effects
  • Erythrocytes / immunology
  • Gene Expression Regulation
  • Graft Survival / drug effects
  • Graft Survival / immunology
  • Humans
  • Immunity, Cellular / drug effects
  • Immunity, Humoral / drug effects
  • Immunosuppression*
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Interleukin-4 / genetics
  • Interleukin-4 / metabolism
  • Lymphocyte Culture Test, Mixed
  • Lymphocytes / drug effects
  • Lymphocytes / immunology
  • Lymphocytes / metabolism*
  • Lymphocytes / pathology
  • Mice
  • Mice, Inbred BALB C
  • Oligopeptides / administration & dosage
  • Oligopeptides / immunology
  • Oligopeptides / pharmacology*
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / immunology
  • Peptide Fragments / pharmacology*
  • Sheep
  • Skin Transplantation

Substances

  • Caseins
  • Oligopeptides
  • Peptide Fragments
  • Val-Glu-Pro-Ile-Gly-Tyr
  • Interleukin-4
  • Interferon-gamma