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Proline-rich Polypeptides (PRPs)

PRPs are probably the most important component in Colostrum. The concentration of PRPs in whole colostrum powder (no PRPs removed) is between 1-3% of the total powder weight. Most manufacturers of colostrum powders remove the PRP fraction, lactose, minerals and water, to elevate the solids content, Immonoglobulin levels and protein content of the powder. This then reduced the medical effectiveness of the colostrum powder. They do this using ultrafiltration technology.

PRPs are generally characterized by PRP1, PRP2, PRP3, and to a lesser level PRP4 and PRP5.

PRP's are also called Transfer Factor, Info-Peptides, Info-Proteins, or Cytokine Precusors. PRP's are hormones that regulates the thymus gland (bodies central command for the immune system), stimulating an under active immune system or down-regulating an overactive immune system as seen in autoimmune disease. PRP inhibit the overproduction of lymphocytes and T-cells.

Chemical Structure

PRP1 is thought to be an inactive class of non-protein nitrogen compounds, with molecular weights between 3,000-5,000 Daltons.

PRP2 (1,500 - 3,000 MW) peptides chains are thought to contain active peptides that are used to modulate cytokine levels in the body particularly IFN-beta or beta-interferon, which have anti-viral properties.

PRP3 (400 - 1,500). PRP3a and PRP3b subclasses contain active peptides chains that modulate the IFN-alpha cytokine levels in the body which is used in modulating auto-immune responses.

Mechanisms of Action

PRPs enhance the ability of the thymus gland to release factors that help regulate immune functions in the body. Specifically, T-cells called Th 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. Thus, PRPs can balance the TH1/TH2 cytokine states in the body, creating homeostasis in the body.

Applications

PRP Functions

• Modulates immune system

PRP promotes T-lymphocyte function [1] and can either stimulate the lymphocytes to become 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, which 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 case of new infection [5]. Suppressor T-cells deactivate other lymphocytes, effectively turning off the immune response to avoid damage to healthy tissue [6]. PRP also stimulates 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].

• Molecular signaling devices

PRP works through specific receptors on cell surfaces [2].

• Stimulates undifferentiated lymphocytes in thymus to become either helper T-cells or suppressor T-cells

PRP from ovine (sheep) colostrum acted as a hormone in the thymus gland by stimulating thymocytes (immature lymphocytes) to differentiate and become activated as either helper T-cells (CD4+) or suppressor T-cells [9]. Helper T-cells are a vital part of the immune response which stimulate the production and differentiation of cytotoxic T-cells and B-cells, attract white blood cells, and stimulate 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.

• Promotes growth and differentiation of B-cells

PRP promotes the growth and differentiation of B-cells, a type of lymphocyte which produces antibodies to antigens, including viral antigens [10].

• Potent stimulator of Natural Killer cell (NK cell) activity by up to 10 times

PRP stimulates 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 which actually attack and kill pathogens. NK cells also attack and kill cancerous cells [11].

• Stimulates the production of tumor necrosis factor-alpha (TNF-α) and interferon-gamma (INF-γ)

PRP stimulates the production of pro-inflammatory cytokines TNF-α and INF-γ, the two major pro-inflammatory cytokines, in white blood cells [12], peritoneal cells [13], and placental and amniotic membranes [14].

• Promotes the proliferation of leukocytes (white blood cells) [15]

• Stimulates production of cytokines by peripheral blood cells

The types of cytokines stimulated by PRP depend on the antigenic stimulation present or the activity state of the immune system (underproductive or overproductive). In one study, mice exposed to Herpes simplex virus (HSV) were stimulated to produce large amounts of IL-2 and INF-γ and small amounts of IL-10, while mice which had been given transfer factor (PRP) prior to infection responded to HSV by secreting INF-γ but no IL-2 [16]. PRP stimulates the production of TNF-α, INF-γ, IL-6 and IL-10 in blood cell cultures [17].

• Induces differentiation and maturation of monocytes and macrophages [18]

• Increases 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. PRP is known to initiate this inflammatory response [19].

• Produces immunity to certain viruses

PRP has been experimentally shown to provide immunity to several viruses, including herpes viruses [20[21][22], Epstein-Barr virus [23], HIV [24], measles [25], vesicular stomatitis virus [26] (a close relative of the rabies virus which is used in experimental systems to study the properties of Rhabdoviruses), and others [27][28].

• Effective against 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. PRP inhibits the replication of both viruses [29][30].

• May help stop the “cytokine storm” seen in bird flu

Influenza A virus subtype H5N1 sets off a so-called “cytokine storm” which usually results in an often fatal respiratory disease in those infected with the virus. Research has indicated that the storm is caused by cytokine dysregulation which allows pro-inflammatory cytokines to be produced in large numbers, setting off a potentially fatal inflammatory response [31]. As PRP is known to down regulate an overactive immune system, it potentially could be used to put a stop to the overproduction of cytokines and restore homeostasis to the body, preventing a fatal outcome. In one case in Thailand, four patients were diagnosed with bird flu. Only one survived – that person had been taking colostrum powder (which contains PRP) prior to infection.

• Clinically proven to increase T-cell count in AIDS to normal or near-normal levels

In clinical studies conducted in the nations of Nigeria, Kenya and Zambia in Africa, where AIDS is a particularly devastating disease, PRP oral spray products were shown to boost T-cell (CD4+) levels to normal or near-normal levels (median 502, none less than 300) in AIDS patients whose T-cell levels prior to treatment were well below normal (median 275). Along with the increase in T-cells came a remission of AIDS symptoms within two days of start of treatment, including nausea, vomiting and diarrhea. In the Nigerian study, weight gains of 5% were recorded. Patients taking the PRP spray fared much better in terms of quality of life than did patients on anti-retroviral drugs [32]. Thus the ability of PRP to stimulate the immune response when it is insufficient by inducing the production of new helper T-cells appears to enable the immune system of AIDS patients to recover sufficiently so that it is able to fight the HIV on its own.

• Not species specific

PRP is not species specific. PRP from bovine milk works on all mammals, including humans, dogs and cats [33].

• Natural product, no known side effects

As PRP is produced by all mammals and is an entirely natural product, there are no known side effects and is completely safe for all ages.

• Can be delivered as a fast acting oral spray

References

{{Proline rich Polypeptides}}

[[Category:Peptides| ]] [[ar:هضميد]] [[bg:Полипептид]] [[ca:Pèptid]] [[cs:Peptid]] [[da:Peptid]] [[de:Peptid]] [[et:Peptiidid]] [[es:Péptido]] [[eo:Peptido]] [[fa:پپتید]] [[fr:Peptide]] [[ko:펩타이드]] [[it:Peptide]] [[he:פפטיד]] [[lt:Polipeptidas]] [[mk:Пептид]] [[ja:ペプチド]] [[no:Peptid]] [[nn:Peptid]] [[pl:Peptydy]] [[pt:Peptídeo]] [[ru:Пептиды]] [[sk:Peptid]] [[fi:Peptidi]] [[sv:Peptid]] [[uk:Пептиди]] [[ur:Peptide]] [[zh:肽]]

1. Zimecki, M, Artym, J. Therapeutic properties of proteins and peptides from colostrum and milk. <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=17407968&dopt=Citation">Post?py Higieny i Medycyny Doswiadczalne j 59:309-323 (2005)</a>.

2. Zimecki, M, Staroscik, K, Janusz, M, Lisowski, J, Wieczorek, Z. The inhibitory activity of a proline-rich polypeptide (PRP) on the immune response to polyvinylpyrrolidone (PVP). <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=6234865&dopt=Citation">Archivum immunologiae et therapiae experimentalis (Warszava) 31(6):895-903 (1983)</a>.

3. Wieczorek, Z, Zimecki, M, Spiegel, K, Lisowski, J, Janusz, M. Differentiation of T cells into helper cells from immature precursors: identification of a target cell for a proline-rich polypeptide (PRP). <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=2534785&dopt=Citation">Archivum immunologiae et therapiae experimentalis (Warszava) 37(3-4):313-322 (1989)</a>. The precursors of helper T cells belong to a minor thymocyte subset bearing the Thy-1 +/-, H-2+, L3T4-, lyt 2-, CD3- phenotype. PRP induced the production of antigens consistent with mature helper T cells

4. Bishop, GA, Haxhinasto, SA, Stunz, LL, Hostager, BS. Antigen-specific B-lymphocyte activation. <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=14584878&dopt=Citation">Critical Reviews in Immunology 23(3):159-197 (2003)</a>. B cells have the exclusive ability to produce and secrete immunoglobulins of various types. They also function in antigen presentation and the production of a number of cytokines and chemokines.

5. 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. <a href="http://www.jleukbio.org/cgi/content/abstract/80/6/1354">Journal of Leukocyte Biology (2006)</a>. CD8+ memory T cell expansion following a second encounter with a pathogen is a hallmark of adaptive immunity. Antigen-specific CD4+ cells, activated by dendritic cells, stimulate the this expansion of CD8+ cells.

6. Zimecki, M, Staroscik, K, Janusz, M, Lisowski, J, Wieczorek, Z. The inhibitory activity of a proline-rich polypeptide (PRP) on the immune response to polyvinylpyrrolidone (PVP). <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=6234865&dopt=Citation">Archivum immunologiae et therapiae experimentalis (Warszava) 31(6):895-903 (1983)</a>.

7. Inglot, A.D., et al. "Colostrinine: a proline-rich polypeptide from ovine colostrum is a modest cytokine inducer in human leukocytes." <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=9017161&dopt=Citation">Arch Immunol Ther Exp (Wasz), 1996;44(4):215-224</a>.

8. Zablocka, A, Janusz, M, Macala, J, Lisowski, J. A proline-rich polypeptide complex and its nonapeptide fragment inhibit nitric oxide production induced in mice. <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=11566627&dopt=Citation">Regulatory Peptides 125(1-3):35-39 (2005)</a>.

9. Wieczorek, Z, Zimecki, M, Spiegel, K, Lisowski, J, Janusz, M. Differentiation of T cells into helper cells from immature precursors: identification of a target cell for a proline-rich polypeptide (PRP). <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=2534785&ordinalpos=34&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum">Archivum immunologiae et therapiae experimentalis (Warszava) 37(3-4):313-322 (1989)</a>.

10. Julius, MH, et al. A colostral protein that induces the growth and differentiation of resting B lymphocytes. <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=3257974&dopt=Citation">Journal of Immunology 140:1366-1371 (1988)</a>. Colostrinin has also been shown to induce the growth and differentiation of resting B lymphocytes. T and B lymphocytes are the two main types of lymphocytes involved in the immune response.

11. See, D, et al. Increased tumor necrosis factor alpha (TNF-alpha) and natural killer cell (NK) function using an integrative approach in late stage cancers. <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=12148949&dopt=Citation">Immunological Investigations 31(2):137-153 (2002)</a>. PRPs are known to increase the production of both TNF-alpha and NK cell activity. This treatment strategy has shown promise in the treatment of terminal cancers.

12. Inglot, A.D., et al. "Colostrinine: a proline-rich polypeptide from ovine colostrum is a modest cytokine inducer in human leukocytes." <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=9017161&dopt=Citation">Arch Immunol Ther Exp (Wasz), 1996;44(4):215-224</a>.

13. Blach-Olszewska, Z, Janusz, M. Stimulatory effect of ovine colostrinine (a proline-rich polypeptide) on interferons and tumor necrosis factor product by murine resident peritoneal cells. <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=9090439&dopt=Citation">Archivum Immunologiae et Therapie Experimentalis (Warsaw) 45(1):43-47 (1997)</a>. Colostrinin stimulates the production of tumor necrosis factor-alpha (TNF-a) and interferon-beta (INF-ß), both important cytokines in the inflammatory response.

14. Domaraczenko, B, Janusz, M, Orzechowska, B, Jarosz, W, Blach-Olszewska, Z. 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. <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=10527824&dopt=Citation">Placenta 20(8):695-701 (1999)</a>.

15. Kruzel, ML, Janusz, M, Lisowski, J, Fischleigh, RV, Georgiades, JA. Towards an understanding of biological role of colostrinin peptides. <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=11859934&dopt=Citation">Journal of Molecular Neuroscience 17(3):379-389 (2001)</a>.

16. Kirkpatrick CH. (1993) Structural nature and function of transfer factors. <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=8363241&dopt=Citation">Annals New York Academy of Sciences. 685:362-8</a>.

17. Zablocka, A, Janusz, M, Macala, J, Lisowski, J. A proline-rich polypeptide complex and its nonapeptide fragment inhibit nitric oxide production induced in mice. <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=11566627&dopt=Citation">Regulatory Peptides 125(1-3):35-39 (2005)</a>.

18. 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. <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=15904991&dopt=Citation">Peptides 26(11):2188-2192 (2005).</a>

19. Janusz M, Lisowski J. (1993) Proline-rich polypeptide (PRP) - an immunomodulatory peptide from ovine colostrum. <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=8010865&dopt=Citation">Archivum Immunologiae et Therapiae Experimentalis. 41:275-279</a>.

20. Pizza, G, Meduri, R, De Vinci, C, Scorolli, L, Viza, D. Transfer factor prevents relapses in herpes keratitis patients: a pilot study. <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=7547082&dopt=Citation">Biotherapy 8(1):63-68 (1994)</a>.

21. Pizza, G, Viza, D, De Vinci, C, Palareti, A, Cuzzocrea, D, Fornarola, V, Baricordi, R. Orally administered HSV-specific transfer factor (TF) prevents genital or labial herpes relapses. <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=8993760&dopt=Citation">Biotherapy 9(1-3):67-72 (1996)</a>.

22. Meduri, R, Campos, E, Scorolli, L, De Vinci, C, Pizza, G, Viza, D. Efficacy of transfer factor in treating patients with recurrent ocular herpes infections. <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=8993759&dopt=Citation">Biotherapy 9(1-3):61-66 (1996)</a>.

23. Prasad, U, bin Jalaludin, MA, Rajadurai, P, Pizza, G, De Vinci, C, Viza, D, Levine, PH. Transfer factor with anti-EBV activity as an adjuvant therapy for nasopharyngeal carcinoma: a pilot study. <a href="http://www.springerlink.com/content/k22l330032723678/">Biotherapy 9(1-3):109-115 (1996)</a>.

24. Raise, E, Guerra, L, Viza, D, Pizza, G, De Vinci, C, Schiattone, ML, Rocaccio, L, Cicognani, M, Gritti, F. Preliminary results in HIV-1-infected patients treated with transfer factor (TF) and zidovudine (ZDV). <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=8993757&dopt=Citation">Biotherapy 9(1-3):49-54 (1996).</a>

25. Ferrer-Argote, VE, Romero-Cabello, R, Hernandez-Mendoza, L, Arista-Viveros, A, Rojo-Medina, J, Balseca-Olivera, F, Fierro, M, Gonzalez-Constandse, R. Successful treatment of severe complicated measles with non-specific transfer factor. <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=7893983&dopt=Citation">In Vivo 8(4):555-557 (1994)</a>.

26. Orzechowska, B., et al. “Antiviral effect of proline-rich polypeptide in murine resident peritoneal cells.” <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=9770073&dopt=Citation">Acta Virol; 1998;42(2):75-78</a>.

27. 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. <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=11242457&dopt=Citation">British Journal of Nutrition 84(Suppl.1):S127-S134 (2000)</a>. Lactoferrin and lactoperoxidase, both present in colostrum in large amounts, provide non-specific defense against a broad spectrum of pathogens, including bacteria and viruses. This is significant both for the protection of commercially important animals as well as humans.

28. Ushijima H, Dairaku M, Mukoyama A. Kansenshogaku <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=2066591&dopt=Citation">Zasshi. 1991 Jan;65(1):54-60</a>. Related Articles, Links,[Bacteriostatic activity of bovine colostrum][Article in Japanese],Department of Enteroviruses, National Institute of Health.

29. Pizza, G, Amadori, M, Ablashi, D, De Vinci, C, Viza, D. (2006). Cell mediated immunity to meet the avian influenza A (H5N1) challenge. <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=16603322&dopt=Citation">Medical Hypoteses 67(3):601-8</a>. As no vaccine can be made ahead of time for a possible bird flu pandemic, cell mediated immunity via specific transfer factor (PRP) may be useful for both the prevention and treatment of infection.

30. De Vinci, C, Levine, PH, Pizza, G, Fudenberg, HH, Orens, P, Pearson, G, Viza, D. Lessons from a pilot study of transfer factor in chronic fatigue syndrome. <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=8993764&dopt=Citation">Biotherapy 9(1-3):87-90 (1996)</a>.

31. Chan, MC, Cheung, CY, Chui, WH, Tsao, SW, Nicholls, JM, Chan, YO, Chan, RW, Long, HT, Poon, LL, Guan, Y, Peiris, JS. Proinflammatory cytokine responses induced by influenza A (H5N1) viruses in primary human alveolar and bronchial epithelial cells. <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=16283933&dopt=Citation">Respiratory Research 6:135 (2005)</a>.

32. Keech, A. Unpublished data. (2006).

33. Khan, A. Non-specificity of transfer factor. <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=855952&dopt=Citationm">Annals of Allergy 38(5):320-322 (1977)</a>.