Colostrinin Decreases Hypersensitivity and Allergic Responses to Common Allergens

Abstract

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.

Effects of Colostrinin™ on gene expression-transcriptomal network analysis

“…These data are in line with the findings that CLN significantly decreased levels of allergen-induced (ragweed pollen and house dust mite extract-specific) IgE/IgG1 levels, as well as mucin levels, and the recruitment of eosinophils in the airways of challenged, sensitized animals [38]. It has been also demonstrated that CLN has no ability to induce IgE antibodies, immediate cutaneous reactions, inflammation, mucin production or airway hyperresponsiveness [38]. Recent findings show that the epithelial gamma-aminobutyric acid (GABA)-ergic system has an essential role in asthma [39].…”

“…Our data suggest that CLN downregulates the expression of the gamma subunit of the Fc epsilon receptor as well as 24 ALDOC↓,ANXA3,ATP1A3↓,ATP1B1,ATP1B3,beta-estradiol,BTG2,CACNB1↓,CCDC80, CCNE2 (includes EG:9134),CDH11,ELK3↓, ERBB2,FLOT1,GPX3↓,HNRPH1↑,HRAS,HSD17B1↑, HTRA1,IGF2R,KRT19,ODF1↓,PBX1,PCDHGA3↓,PDIA4,RASA3↓,SC4MOL,SPAG4, SPINK4↓, TERT,THSD1↑,TMSB4X,TOP2A,TSC22D1,TSC22D4↓ 13 Cancer Reproductive system disease Tumor morphology 25 ADAMTS13↓,AMD1,ANGPT2,ANGPTL4↓,ANXA5,ATF1,CDC25B,CHRNB1,CLU,DST, ELAVL1,ETS2,F2,F8↓,GREM1,LAMP1,LENEP↓, LGMN↑,MSN,MYBL2,MYC,NFYB, POLR3D↑,PRPH↓,PRPH2↑,PRRG2↓,RFX1,ROM1,SLIT1↓,SNX2,SNX6↑,TADA2L↓,TGFBR2, TGFBRAP1↑,TOP2A 13 Cell death Digestive system development and function Tissue development JNK, protein kinase C (PKC), phospholipase A2 (cPLA2), and interleukin 13 (IL-13) expression. These data are in line with the findings that CLN significantly decreased levels of allergen-induced (ragweed pollen and house dust mite extract-specific) IgE/IgG1 levels, as well as mucin levels, and the recruitment of eosinophils in the airways of challenged, sensitized animals [38]. It has been also demonstrated that CLN has no ability to induce IgE antibodies, immediate cutaneous reactions, inflammation, mucin production or airway hyperresponsiveness [38].…”

“…However, we speculate that by doing so CLN affects inflammatory processes as shown previously [38]. There is overwhelming evidence showing that ROS are enhancers of growth factor-and cytokine-induced signaling pathways.…”

“…CLN consistently down-regulates GAD and GABAARs in epithelial cells. These data strongly suggest that this could be the molecular mechanism by which CLN prevented the development of airway inflammation, hyperresponsiveness and mucin production in a mouse model of asthma [38]. It could be proposed that CLN administration may result in suppression of asthma symptoms via selective inhibition of GABAAR and the GABA synthetic enzyme glutamic acid decarboxylase.…”

Colostrinin™: a naturally occurring compound derived from mammalian colostrum with efficacy in treatment of neurodegenerative diseases, including Alzheimer's

“…It affects cytokine induction [15,16] and amyloid β plaque formation, is believed to be an immunomodulator [16] and plays a role in the homeostasis of cellular redox and signal transduction. It also protects against spontaneous and induced mutations [17] , decreases allergic inflammation [18] , induces neurite outgrowth in cultured cells [19] , increases the lifespan of cultured cells by preventing mitochondrial dysfunction [20] and protects against amyloid-β -induced apoptosis in neuroblastoma cells [21] . A recent article investigating the mechanisms of the action of CLN, published in the Journal of Alzheimer's Disease [2] , reviewed the utility of CLN in the maintenance of physiological processes where oxidative stress has a causative role.…”