Investigating the effect of pegylated granulocyte colony stimulating factor therapy on experimental mastitis in lactating Holsteins

Abstract

Abstract Mastitis dominates dairy economic and health concerns. Neutrophils are the most prominent cellular defense against mastitis causing pathogens making neutrophil expansion and activation, prime candidates for targeted therapeutics. The granulocyte colony-stimulating factor (gCSF) cytokine targets neutrophil differentiation and causes neutrophilia. Recently pegylated (PEG) gCSF has been shown to decrease naturally-occurring cases of mastitis. To better understand the mechanisms employed by PEG-gCSF to reduces mastitis incidence we have evaluated PEG-gCSF in an experimental mastitis challenge. We challenged 11 lactating Holsteins with Escherichia coli by intra-mammary infusion. Cows received injections of PEG-gCSF 14 days and 7 days, prior to disease challenge. While somatic cell counts in the milk did not differ between treated and non-treated animals, the treated cows had lower bacterial counts in the 48 hours post infection (P < 0.05). Bovine serum albumin levels in milk, a measure of disease severity, were also lower 24 hours post challenge for PEG-gCSF treated animals. Post challenge, control cattle had reduced milk yield (P = 0.05) and a lower percent feed intake (P < 0.01) compared to treated cows. PEG-gCSF treated cattle significantly increased circulating levels of neutrophils (P < 0.01), as well as monocyte and lymphocyte responses (P < 0.05). We demonstrated that PEG-gCSF treated cattle had reduced disease severity and have begun to further elucidate the mechanism of neutrophil immune responses. This data suggests the utilization of PEG-gCSF as a potential antibiotic alternative to mastitis treatment and prevention and supports neutrophil focused therapies as an important facet of mastitis disease protection.