Dynamic Chiropractic – July 16, 2007, Vol. 25, Issue 15
The Physiological Functions of Proline-Rich Polypeptides (PRPs)
By John Maher, DC, DCBCN, BCIM
Bovine or ovine colostrum, especially when taken from the first two milkings, is rich in protein subfractions (called immunoglobulins), which provide passive immunity benefits. Properly processed, it also can be rich in proline-rich polypeptides (PRPs), which are nanosized chains of 10 amino acids or less (notably praline) that have a very powerful effect in actively modulating immune responses in mammals.
PRPs enhance the ability of the thymus gland to release factors that help regulate immune functions in the body. Specifically, T-cells called Th1 helper cells are antagonists to the activity of Th2 helper cells. Th2 promotes B-lymphocyte functions. PRP can induce a shift from a predominantly humeral immune response to a more protective cellular response, described as a "Th2 to Th1 shift." This shift may assist the immune system in more effectively fighting chronic viral and bacterial infections, while simultaneously inhibiting the initiation of inappropriate inflammatory cascades associated with allergy, chemical sensitivity and autoimmune responses.
Here is a more detailed list of the physiological functions of PRPs:
- Modulate the immune system. PRPs promote T-lymphocyte function1 and can stimulate the lymphocytes to become either helper T-cells or suppressor T-cells.2,3 Helper T-cells activate B-lymphocytes by presenting an antigen, such as a viral protein, to the B-cell. The B-cell then produces antibodies to that protein.4 Helper T-cells also help produce memory T-cells, which retain the "memory" of the antigen to shorten the response time in cases of new infection.5 Suppressor T-cells deactivate other lymphocytes, effectively turning off the immune response to avoid damage to healthy tissue.6 PRPs also stimulate the production of a whole range of cytokines, particularly the pro-inflammatory cytokines TNF-α and INF-γ,7 and the anti-inflammatory cytokines IL-6 and IL-10.8
- Act as molecular signaling devices, working through specific receptors on cell surfaces.2
- Stimulate undifferentiated lymphocytes in thymus to become either helper T-cells or suppressor T-cells. PRPs act as a hormone in the thymus gland by stimulating thymocytes (immature lymphocytes) to differentiate and become either helper T-cells or suppressor T-cells.9 Helper T-cells are a vital part of the immune response that stimulates the production and differentiation of cytotoxic T-cells and B-cells, attracts white blood cells, and stimulates macrophages to engulf and destroy pathogens. Suppressor T-cells inhibit the production of cytotoxic T-cells to prevent tissue damage and suppress the immune response, when no longer needed.
- Promote growth and differentiation of B-cells. PRPs promote the growth and differentiation of B-cells, a type of lymphocyte which produces antibodies to antigens, including viral antigens.10
- Stimulate Natural Killer cell (NK cell) activity. PRPs stimulate the activity of NK cells up to 10 times, far greater than any other known substance. NK cells, along with cytotoxic T-cells, are the cells that actually attack and kill pathogens. NK cells also attack and kill cancerous cells.11
- Stimulate the production of tumor necrosis factor-alpha (TNF-α) and interferon-gamma (INF-γ). PRPs stimulate production of the two major pro-inflammatory cytokines, TNF-α and INF-γ, in white blood cells,12 peritoneal cells,13 and placental and amniotic membranes.14
- Promote the proliferation of leukocytes (white blood cells).15
- Stimulate production of cytokines by peripheral blood cells. The types of cytokines stimulated by PRPs depend on the antigenic stimulation present or the activity state of the immune system (underproductive or overproductive).
- Induce differentiation and maturation of monocytes and macrophages.16
- Increase the permeability of blood vessels in the skin. Part of the inflammatory response to infection is an increase in the permeability of blood vessels in the skin, to allow the passage of blood cells and cytokines into the connective tissue to combat the infection. PRPs are known to initiate this inflammatory response.17
- Produce immunity to certain viruses. PRPs have been experimentally shown to provide immunity to several viruses, including herpes viruses,18,19,20 Epstein-Barr virus,21 HIV,22 measles,23 vesicular stomatitis virus24 and others.25,26
- Inhibit viruses known to be associated with autoimmune diseases. Epstein-Barr virus and human herpes virus-6 (HHV-6) have been associated with chronic fatigue syndrome, an autoimmune disorder. PRPs inhibit the replication of both viruses.27,28
- Increase T-cell count in AIDS to normal or near-normal levels. In clinical studies conducted in Nigeria, Kenya and Zambia, PRP oral-spray products were shown to boost T-cell (CD4+) levels to normal or near-normal levels in AIDS patients whose T-cell levels were well below normal. Along with the increase in T-cells came a remission of AIDS symptoms (including nausea, vomiting and diarrhea) within two days of start of treatment. In the Nigerian study, weight gains of 5 percent were recorded. Patients taking the PRP spray fared much better in terms of quality of life than did patients on anti-retroviral drugs.29 Thus, the ability of PRPs to stimulate insufficient immune response by inducing the production of new helper T-cells may enable the immune systems of AIDS patients to recover sufficiently to fight the HIV on their own.
PRPs are not species-specific. PRPs from bovine milk work on all mammals, including humans, dogs and cats.30 As PRPs are produced by all mammals and are entirely natural, it is generally thought to be safe for all ages. However, lactose is usually associated with PRP; therefore, those with milk intolerance may need to proceed with caution. The addition of lactase, the milk sugar digesting enzyme, may ameliorate lactose intolerance.
Also, delicate immune system changes occur following conception and during pregnancy. Specifically, there is a shift to Th2 dominance to inhibit the mother's immune system from over-responding to the different DNA of the new life now inside her. Although there are no known reports of colostrum's interference with full and normal gestation, until further investigation assures safety, it is suggested that pregnant women should avoid PRP-rich colostrum products unless recommended by their doctor.
Furthermore, PRPs, being such small peptides, can easily be denatured by the digestive acids and enzymes. As such, they are often taken as a sublingual spray. To be taken as a functional food, it is likely best to protect the peptides in liposomes, which are submicron and nanosized lipid spheres, usually made of milk fats or phosphatidyl choline. Using such technologies, extra PRPs also can be added to colostrum to make the colostrum especially high in bioavailable PRPs.
- Zimecki M, Artym J. [Therapeutic properties of proteins and peptides from colostrum and milk.] Postepy Hig Med Dow (Online), 2005;59:309-23.
- Janusz M, Staroscik K, Zimecki M, et al. A proline-rich polypeptide (PRP) with immunoregulatory properties isolated from ovine colostrum. Murine thymocytes have on their surface a receptor specific for PRP. Arch Immunol Ther Exp (Warsz), 1986;34(4):427-36.
- Wieczorek Z, Zimecki M, Spiegel K, et al. Differentiation of T cells into helper cells from immature precursors: identification of a target cell for a proline-rich polypeptide (PRP). Arch Immunol Ther Exp (Warsz), 1989;37(3-4):313-22.
- Bishop GA, Haxhinasto SA, Stunz LL, Hostager BS. Antigen-specific B-lymphocyte activation. Crit Rev Immunol, 2003;23(3):149-97.
- Shi M, Hao S, Chan T, Xiang J. CD4+ T cells stimulate memory CD8+ T cell expansion via acquired pMHC I complexes and costimulatory molecules, and IL-2 secretion. J Leukoc Biol, 2006;80(6):1354-63.
- Zimecki M, Staroscik K, Janusz M, et al. The inhibitory activity of a proline-rich polypeptide (PRP) on the immune response to polyvinylpyrrolidone (PVP). Arch Immunol Ther Exp (Warsz), 1983;31(6):895-903.
- Inglot AD, Janusz M, Lisowski J. Colostrinine: a proline-rich polypeptide from ovine colostrum is a modest cytokine inducer in human leukocytes. Arch Immunol Ther Exp (Warsz), 1996;44(4):215-24.
- Zablocka A, Janusz M, Rybka K, et al. Cytokine-inducing activity of a proline-rich polypeptide complex (PRP) from ovine colostrum and its active nonapeptide fragment analogs. Eur Cytokine Netw, 2001;12(3):462-7.
- Wieczorek Z, et al., 1996, op. cit.
- Julius MH, Janusz M, Lisowski J. A colostral protein that induces the growth and differentiation of resting B lymphocytes. J Immunol, 1988;140(5):1366-371.
- See DM, Khemka P, Sahl L, et al. The role of natural killer cells in viral infections. Scand J Immunol, 1997;46(3):217-24.
- Inglot AD, et al., 1996, op. cit.
- Blach-Olszewska Z, Janusz M. Stimulatory effect of ovine colostrinine (a proline-rich polypeptide) on interferons and tumor necrosis factor production by murine resident peritoneal cells. Arch Immunol Ther Exp (Warsz), 1997;45(1):43-7.
- Domaraczenko B, Janusz M, Orzechowska B, et al. Effect of proline rich polypeptide from ovine colostrum on virus replication in human placenta and amniotic membrane at term; possible role of endogenous tumor necrosis factor alpha. Placenta, 1999;20(8):695-701.
- Kruzel ML, Janusz M, Lisowski J, et al. Towards an understanding of biological role of colostrinin peptides. J Mol Neurosci, 2001;17(3):379-89.
- Kubis A, Marcinkowska E, Janusz M, Lisowski J. Studies on the mechanism of action of a proline-rich polypeptide complex (PRP): effect on the stage of cell differentiation. Peptides, 2005;26(11):2188-92.
- Janusz M, Lisowski J. Proline-rich polypeptide (PRP) - an immunomodulatory peptide from ovine colostrum. Arch Immunol Ther Exp (Warsz), 1993;41(5-6):275-9.
- Pizza G, Meduri R, De Vinci C, et al. Transfer factor prevents relapses in herpes keratitis patients: a pilot study. Biotherapy, 1994;8(1):63-8.
- Pizza G, Viza D, De Vinci C, et al. Orally administered HSV-specific transfer factor (TF) prevents genital or labial herpes relapses. Biotherapy, 1996;9(1-3):67-72.
- Meduri R, Campos E, Scorolli L, et al. Efficacy of transfer factor in treating patients with recurrent ocular herpes infections. Biotherapy, 1996;9(1-3):61-6.
- Prasad U, bin Jalaludin MA, Rajadurai P, et al. Transfer factor with anti-EBV activity as an adjuvant therapy for nasopharyngeal carcinoma: a pilot study. Biotherapy, 1996;9(1-3):109-15.
- Raise E, Guerra L, Viza D, et al. Preliminary results in HIV-1-infected patients treated with transfer factor (TF) and zidovudine (ZDV). Biotherapy, 1996;9(1-3):49-54.
- Ferrer-Argote VE, Romero-Cabello R, Hernandez-Mendoza L, et al. Successful treatment of severe complicated measles with non-specific transfer factor. In Vivo, 1994;8(4):555-7.
- Orzechowska B, Janusz M, Domaraczenko B, Blach-Olszewska Z. Antiviral effect of proline-rich polypeptide in murine resident peritoneal cells. Acta Virol, 1998;42(2):75-8.
- Van Hooijdonk AC, Kussendrager KD, Steijns JM. In vivo antimicrobial and antiviral activity of components in bovine milk and colostrum involved in non-specific defense. Br J Nutr, 2000;84(Suppl 1):S127-34.
- Ushijima H, Dairaku M, Honnma H, et al. [Immunoglobulin components and anti-viral activities in bovine colostrum.] Kansenshogaku Zasshi, 1990;64(3):274-9.
- Ablashi DV, Levine PH, De Vinci C, et al. Use of anti HHV-6 transfer factor for the treatment of two patients with chronic fatigue syndrome (CFS). Two case reports. Biotherapy, 1996;9(1-3):81-6.
- De Vinci C, Levine PH, Pizza G, et al. Lessons from a pilot study of transfer factor in chronic fatigue syndrome. Biotherapy, 1996;9(1-3):87-90.
- Keech A. Unpublished data. (2006).
- Khan A. Non-specificity of transfer factor. Ann Allergy, 1977;38(5):320-2.
for previous articles by John Maher, DC, DCBCN, BCIM.