A commercial immune modulating feed additive restores L-selectin and CCL5 expression following dexamethasone treatment of murine immune cells in a MyD88-dependent manner

Abstract

Bovine mastitis costs the dairy industry billions of dollars every year and presents a health challenge in dairy facilities. Immunosuppressive effects of the periparturient period increase the incidence of mastitis. During this time, cattle experience an elevation in circulating cortisol, which reduces polymorphonuclear cell function and ability to clear infection. OmniGen-AF (OMN; Phibro Animal Health, Teaneck, NJ) is an immunomodulatory feed additive that alters gene expression and is used to reduce rates of mastitis. We hypothesized that OMN restores gene expression during periods of immune stress through inhibiting the suppressive effects of glucocorticoid receptor signaling on Toll-like receptor signaling. To test our hypothesis, wild-type (WT) or MyD88 knockout mice were supplemented with OMN and challenged with lipopolysaccharide following dexamethasone (Dex) treatment. Polymorphonuclear cell and macrophage RNA was isolated from intraperitoneal lavages and analyzed for gene expression profiles. Treatment of mice with Dex suppressed expression of l-selectin and CCL5 as compared with phosphate-buffered saline treatment of WT mice. Expression of l-selectin and CCL5 was significantly reduced with Dex treatment in control-fed but not OMN-supplemented WT mice. The protective effect of OMN supplementation on l-selectin expression during Dex treatment was abolished in MyD88 knockout mice. These results suggest that OMN supplementation restores responses of certain genes suppressed by Dex in immune cells in a MyD88-dependent manner. Future research will determine the specific Toll-like receptors, transcription factors, and biochemical properties of OMN that restore gene expression in immunosuppressed cells.

Effect of an Immunomodulatory Feed Additive in Mitigating the Stress Responses in Lactating Dairy Cows to a High Concentrate Diet Challenge

“…Brandão et al [ 26 ] administered LPS to lactating cows and found greater levels of haptoglobin and tumor necrosis factor alpha when animals were fed OMN. Ortiz-Marty et al [ 27 ] reported maintained neutrophil function in OMN fed mice during a dexamethasone and LPS challenge. Dry cows fed OMN during heat stress had greater mammary gland tissue regeneration and produced more milk [ 28 ].…”

“…Despite the evidence of OMN supplementation effects listed in previous studies [ 26 , 27 , 28 , 29 ], to our knowledge, no studies have analyzed the effects of this immunomodulant product in lactating dairy cows exposed to a high concentrate diet challenge in a longitudinal trial. The aim of our study was therefore to study the mitigation effects in zootechnical and immunological parameters.…”

Response to adrenocorticotropic hormone or corticotrophin-releasing hormone and vasopressin in lactating cows fed an immunomodulatory supplement under thermoneutral or acute heat stress conditions

“…The on-dairy prestudy period was needed to elicit an immune response to OG before arrival at the University of Arizona Agricultural Research Complex. Previous studies have established that prefeeding OG for 45 d before the administration of a stress was necessary to demonstrate differences in markers of immune function (Wang et al, 2004;Ryman et al, 2013;Ortiz-Marty et al, 2017). In this study, 506 lactating Holstein cows from a commercial dairy (Caballero Dairy, Eloy, AZ) were separated into 2 groups and fed either the basal silage-based diet (control, CON; n = 252 cows) or the basal diet plus the supplement (OG, 56 g/h per day; n = 254 cows).…”