A host-associated antimicrobial agent exhibits both immunoprotective and immunotherapeutic effects

Abstract

Abstract Inflammation is a critical component of both the defense against injury and the pathophysiology of disease. 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. Given the impact of host response to disease on the health of humans and food animals alike, we examined the effects of supplemental bovine lactoferrin (bLF) and its functional peptide lactoferricin B (LFcin B), on the dysregulated immune response to lipopolysaccharide (LPS). We hypothesized that these antibiotic agents have therapeutic value as low-risk anti-inflammatory agents, a characteristic that is attributable to their regulatory role on intracellular signaling in innate cells. Although present in colostrum, saliva and mucosal secretions, bLF is notably at its highest concentration in the secondary granules of neutrophils. In the host, the 25 AA peptide LFcin B is released following the activity of proteolytic enzymes in the stomach as well as at sites of infection. Viable peripheral monocytes and neutrophils were isolated from calves and stimulated in vitro with LPS, in the presence or absence of bLF/LFcin B. Samples were analyzed using qRT-PCR, Meso Scale Discovery Electrochemiluminescence, immunoprecipitation and western immunoblot detection. The effects of bLF and LFcin B on pro-inflammatory cytokine and inflammatory mediator production will be expressed as the mean ± SD and will be considered significant at P<0.05. Although each exerted differential effects, the p38 MAP kinase pathway appears to be a likely target.