Free and bound cortisol, corticosterone, and metabolic adaptations during the early inflammatory response to an intramammary lipopolysaccharide challenge in dairy cows

Glucocorticoids, particularly cortisol and corticosterone, are key homeostatic regulators during metabolic and endocrine adaptations including inflammatory responses. Besides the established response of total cortisol (TC) concentrations during inflammatory processes in dairy cows, we investigated changes of corticosterone, free cortisol (FC), and serum albumin as the main protein of unspecific cortisol binding, in response to an intramammary lipopolysaccharide (LPS) challenge. Furthermore, we evaluated relationships of glucocorticoid responses with concomitant alterations of metabolites and their endocrine regulators, insulin and glucagon. Blood samples of 10 multiparous Holstein dairy cows (26.8 ± 3.4 d in milk, previous lactation yield: 7,601 ± 938 kg; mean ± SD) were obtained every 30 min up to 5 h after the LPS instillation, and rectal temperature and heart rate were measured in parallel. Corticosterone was measured by enzyme immunoassay, TC by radioimmunoassay, and the proportion of FC by ultrafiltration. A mixed model was used to evaluate differences within the investigated parameters among selected time points (0, 3.5, and 5 h relative to the intramammary LPS administration). Rectal temperature increased up to 41.6 ± 0.1°C at 5 h after the LPS application. Concentrations of TC and corticosterone increased until 3.5 h, and the proportion of FC relative to TC more than doubled until 3.5 h after LPS administration. Serum albumin concentration was reduced at 5 h compared with initial values, whereas concentrations of insulin, glucagon, and glucose were increased after 5 h compared with 0 h. In conclusion, the stimulation of the immune system by the intramammary LPS administration is accompanied by distinct metabolic and endocrine changes. Corticosterone and TC concentrations react similarly in response to the LPS challenge and earlier compared with metabolic adaptations. The increased need of active cortisol is covered by both increased secretion and a higher percentage of FC.