A novel host-associated non-traditional antimicrobial agent, exhibits immune regulatory function

Authors: DAWES, MAISIE - Western University Of Health Sciences; XIE, CHEN - Western University Of Health Sciences; Chitko-Mckown, Carol

Submitted to: Research Workers in Animal Diseases Conference Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 11/6/2018
Publication Date: 12/4/2018
Citation: Dawes, M.E., Xie, C., Chitko-McKown, C.G. 2018. A novel host-associated non-traditional antimicrobial agent, exhibits immune regulatory function [abstract]. Conference of Research Workers in Animal Diseases, December 2-4, 2018, Chicago, Illinois. Abstract #189.

Interpretive Summary:

Technical Abstract: Although inflammation is a critical component of host defense against infectious pathogens and injury, it is also integrally involved in the pathophysiology of disease. Given the impact of the latter on the health of humans and food animals alike, we examined the impact of bovine lactoferrin (bLF) a non-antibiotic antimicrobial, on the systemic dysregulated response of the host immune system to lipopolysaccharide. Lactoferricin B (LFcin B), its functional peptide, was also examined. We hypothesized that the immune-modulating effects of bLF are attributable to its ability to regulate the activation of bioactive proteins involved in innate intracellular signaling. Despite advances in anti-inflammatory therapy and critical care, Gram-negative infections remain a significant cause of mortality in multiple species, and are a primary cause of diarrhea, endotoxemia, sepsis and ultimately death in neonatal calves. We therefore intend to demonstrate that both bLF and LFcin B, each with proven antibiotic effects, also have therapeutic value as low-risk anti-inflammatory agents. Bovine LF, which is present in colostrum, has been demonstrated in saliva and mucosal secretions, and is notably at its highest concentration in the secondary granules of neutrophils. While LFcin B is produced in the stomach following oral bLF supplementation, its action at sites of infection, is believed to be facilitated by the action of proteolytic enzymes. Methods: Viable peripheral bovine monocytes and neutrophils (PMNs) were isolated from calves and stimulated in vitro in the presence or absence of bLF/LFcin B. Samples were analyzed using qRT-PCR, Meso Scale Discovery Electrochemiluminescence, immunoprecipitation and western immunoblot detection. Results will be expressed as the mean ± SE. Values will be considered significant at P<0.05. Results: Both bLF and LFcin B, have immunomodulatory, yet differential effects on inflammatory mediator production. While evidence suggests p38 MAP kinase is a potential target, further investigation into their mechanistic rationale is warranted.