Background: Colostrinin™ (CLN), isolated from mothers’ pre-milk fluid (colostrum), is a uniform mixture of low-molecular-weight, proline-rich polypeptides. CLN induces neurite outgrowth of pheochromocytoma cells, extends the lifespan of diploid fibroblast cells, inhibits β-amyloid-induced apoptosis and improves cognitive functions when administered to Alzheimer’s disease patients. Objective: The aim of this study was to investigate potential allergic responses to CLN and its impact on allergic sensitization and inflammation caused by common allergens. Methods: We used a well-characterized mouse model of allergic airway inflammation. Changes in IgE/IgG1 and mucin levels, airway eosinophilia and hyperreactivity to methacholine were determined by ELISA, differential cell counting and whole-body plethysmography, respectively. Results: CLN did not increase IgE/IgG1 levels or induce cutaneous hypersensitivity reaction, airway inflammation and mucin production. Importantly, CLN significantly (p < 0.001) decreased IgE/IgG1 production, airway eosinophilia, mucin production and hypersensitivity induced by allergenic extracts from ragweed pollen grains and house dust mites. Conclusion: CLN itself is non-allergenic; however, it is effective in preventing allergic responses to known indoor and outdoor allergens. These data support the safe application of CLN and its potential use in the prevention of allergic inflammation in humans.

1.
Janusz M, Lisowski J, Franek F: Isolation and characterization of a proline-rich polypeptide from ovine colostrum. FEBS Lett 1974;49:276–279.
2.
Janusz M, Staroscik K, Zimecki M, Wieczorek Z, Lisowski J: Chemical and physical characterization of a proline-rich polypeptide from sheep colostrum. Biochem J 1981;199:9–15.
3.
Janusz M, Lisowski J: Proline-rich polypeptide (PRP) – an immunomodulatory peptide from ovine colostrum. Arch Immunol Ther Exp (Warsz) 1993;41:275–279.
4.
Kruzel ML, Janusz M, Lisowski J, Fischleigh RV, Georgiades JA: Towards an understanding of biological role of colostrinin peptides. J Mol Neurosci 2001;17:379–389.
5.
Kruzel ML, Polanowski A, Wilusz T, et al: The alcohol-induced conformational changes in casein micelles: a new challenge for the purification of colostrinin. Protein J 2004;23:127–133.
6.
Zimecki M, Lisowski J, Hraba T, Wieczorek Z, Janusz M, Staroscik K: The effect of a proline-rich polypeptide (PRP) on the humoral immune response. 1. Distinct effect of PRP on the T cell properties of mouse glass-nonadherent (NAT) and glass-adherent (GAT) thymocytes in thymectomized mice. Arch Immunol Ther Exp (Warsz) 1984;32:191–196.
7.
Stanton G, Boldogh I, Georgiades JA, Hughes TK: Induction of cell proliferation and cytokines by colostrinin and component proline-rich peptides in human peripheral blood leukocytes. Psychogeriat Ann 2001;4:67–75.
8.
Boldogh I, Liebenthal D, Hughes TK, et al: Modulation of 4HNE-mediated signaling by proline-rich peptides from ovine colostrum. J Mol Neurosci 2003;20:125–134.
9.
Bacsi A, Stanton GJ, Hughes TK, Kruze M, Boldogh I: Colostrinin-driven neurite outgrowth requires p53 activation in PC12 cells. Cell Mol Neurobiol 2005;25:1123–1139.
10.
Schuster D, Rajendran A, Hui SW, Nicotera T, Srikrishnan T, Kruzel ML: Protective effect of colostrinin on neuroblastoma cell survival is due to reduced aggregation of beta-amyloid. Neuropeptides 2005;39:419–426.
11.
Bacsi A, Woodberry M, Kruzel ML, Boldogh I: Colostrinin delays the onset of proliferative senescence of diploid murine fibroblast cells. Neuropeptides 2007;41:93–101.
12.
Leszek J, Inglot AD, Janusz M, Lisowski J, Krukowska K, Georgiades JA: Colostrinin: a proline-rich polypeptide (PRP) complex isolated from ovine colostrum for treatment of Alzheimer’s disease. A double-blind, placebo-controlled study. Arch Immunol Ther Exp (Warsz) 1999;47:377–385.
13.
Leszek J, Inglot AD, Janusz M, et al: Colostrinin proline-rich polypeptide complex from ovine colostrum – a long-term study of its efficacy in Alzheimer’s disease. Med Sci Monit 2002;8:PI93–PI96.
14.
Bilikiewicz A, Gaus W: Colostrinin (a naturally occurring, proline-rich, polypeptide mixture) in the treatment of Alzheimer’s disease. J Alzheimers Dis 2004;6:17–26.
15.
Umetsu DT, Dekruyff RH: Immune dysregulation in asthma. Curr Opin Immunol 2006;18:727–732.
16.
Larche M, Robinson DS, Kay AB: The role of T lymphocytes in the pathogenesis of asthma. J Allergy Clin Immunol 2003;111:450–463; quiz 464.
17.
Keet CA, Wood RA: Food allergy and anaphylaxis. Immunol Allergy Clin North Am 2007;27:193–212.
18.
Cantani A, Micera M: Natural history of cow’s milk allergy. An eight-year follow-up study in 115 atopic children. Eur Rev Med Pharmacol Sci 2004;8:153–164.
19.
Saarinen KM, Pelkonen AS, Makela MJ, Savilahti E: Clinical course and prognosis of cow’s milk allergy are dependent on milk-specific IgE status. J Allergy Clin Immunol 2005;116:869–875.
20.
Simpson AB, Glutting J, Yousef E: Food allergy and asthma morbidity in children. Pediatr Pulmonol 2007;42:489–495.
21.
Boldogh I, Bacsi A, Choudhury BK, et al: ROS generated by pollen NADPH oxidase provide a signal that augments antigen-induced allergic airway inflammation. J Clin Invest 2005;115:2169–2179.
22.
Bacsi A, Choudhury BK, Dharajiya N, Sur S, Boldogh I: Subpollen particles: carriers of allergenic proteins and oxidases. J Allergy Clin Immunol 2006;118:844–850.
23.
Bacsi A, Dharajiya N, Choudhury BK, Sur S, Boldogh I: Effect of pollen-mediated oxidative stress on immediate hypersensitivity reactions and late-phase inflammation in allergic conjunctivitis. J Allergy Clin Immunol 2005;116:836–843.
24.
Sur S, Wild JS, Choudhury BK, Sur N, Alam R, Klinman DM: Long-term prevention of allergic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides. J Immunol 1999;162:6284–6293.
25.
Kruzel ML, Bacsi A, Choudhury B, Sur S, Boldogh I: Lactoferrin decreases pollen antigen-induced allergic airway inflammation in a murine model of asthma. Immunology 2006;119:159–166.
26.
Saloga J, Renz H, Lack G, et al: Development and transfer of immediate cutaneous hypersensitivity in mice exposed to aerosolized antigen. J Clin Invest 1993;91:133–140.
27.
Wolvers DA, van Herpen-Broekmans WM, Logman MH, van der Wielen RP, Albers R: Effect of a mixture of micronutrients, but not of bovine colostrum concentrate, on immune function parameters in healthy volunteers: a randomized placebo-controlled study. Nutr J 2006;5:28.
28.
Sjogren YM, Duchen K, Lindh F, Bjorksten B, Sverremark-Ekstrom E: Neutral oligosaccharides in colostrum in relation to maternal allergy and allergy development in children up to 18 months of age. Pediatr Allergy Immunol 2007;18:20–26.
29.
Sutton BJ, Gould HJ: The human IgE network. Nature 1993;366:421–428.
30.
Miyajima I, Dombrowicz D, Martin TR, Ravetch JV, Kinet JP, Galli SJ: Systemic anaphylaxis in the mouse can be mediated largely through IgG1 and Fc gammaRIII. Assessment of the cardiopulmonary changes, mast cell degranulation, and death associated with active or IgE- or IgG1-dependent passive anaphylaxis. J Clin Invest 1997;99:901–914.
31.
Dombrowicz D, Flamand V, Brigman KK, Koller BH, Kinet JP: Abolition of anaphylaxis by targeted disruption of the high affinity immunoglobulin E receptor alpha chain gene. Cell 1993;75:969–976.
32.
Saini SS, MacGlashan D: How IgE upregulates the allergic response. Curr Opin Immunol 2002;14:694–697.
33.
Spieksma FT, Dieges PH: The history of the finding of the house dust mite. J Allergy Clin Immunol 2004;113:573–576.
34.
Taramarcaz P, Lambelet B, Clot B, Keimer C, Hauser C: Ragweed (Ambrosia) progression and its health risks: will Switzerland resist this invasion? Swiss Med Wkly 2005;135:538–548.
35.
Wopfner N, Gadermaier G, Egger M, et al: The spectrum of allergens in ragweed and mugwort pollen. Int Arch Allergy Immunol 2005;138:337–346.
36.
Tovey ER, Chapman MD, Platts-Mills TA: Mite faeces are a major source of house dust allergens. Nature 1981;289:592–593.
37.
de Blay F, Pauli G, Velten M, Bessot JC: Influence of mite exposure on symptoms of mite-sensitive patients with asthma. J Allergy Clin Immunol 1994;93:136–138.
38.
Bousquet J: Global initiative for asthma (GINA) and its objectives. Clin Exp Allergy 2000;30(suppl 1):2–5.
39.
Zablocka A, Janusz M, Macala J, Lisowski J: A proline-rich polypeptide complex (PRP) isolated from ovine colostrum. Modulation of H(2)O(2) and cytokine induction in human leukocytes. Int Immunopharmacol 2007;7:981–988.
40.
Zablocka A, Janusz M, Rybka K, Wirkus-Romanowska I, Kupryszewski G, Lisowski J: Cytokine-inducing activity of a proline-rich polypeptide complex (PRP) from ovine colostrum and its active nonapeptide fragment analogs. Eur Cytokine Netw 2001;12:462–467.
41.
Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL: Two types of murine helper T cell clone. 1. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 1986;136:2348–2357.
42.
Renz H, Lack G, Saloga J, et al: Inhibition of IgE production and normalization of airways responsiveness by sensitized CD8 T cells in a mouse model of allergen-induced sensitization. J Immunol 1994;152:351–360.
43.
Finkelman FD, Katona IM, Mosmann TR, Coffman RL: IFN-gamma regulates the isotypes of Ig secreted during in vivo humoral immune responses. J Immunol 1988;140:1022–1027.
44.
Deaton CM: The role of oxidative stress in an equine model of human asthma. Redox Rep 2006;11:46–52.
45.
Mak JC, Chan-Yeung MM: Reactive oxidant species in asthma. Curr Opin Pulm Med 2006;12:7–11.
46.
Bacsi A, Aguilera-Aguirre L, German P, Kruzel ML, Boldogh I: Colostrinin decreases spontaneous and induced mutation frequencies at the hprt locus in Chinese hamster V79 cells. J Exp Ther Oncol 2006;5:249–259.
47.
Kauffman HF, Tomee JF, van de Riet MA, Timmerman AJ, Borger P: Protease-dependent activation of epithelial cells by fungal allergens leads to morphologic changes and cytokine production. J Allergy Clin Immunol 2000;105:1185–1193.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.