Acute phase response in lactating dairy cows after intramammary LPS administration during long-term hyperinsulinemic hypoglycemic and hyperinsulinemic euglycemic clamps

Dairy cows undergo considerable metabolic and physiological changes during the transition from pregnancy to lactation. They may contribute to the development of metabolic and infectious diseases, which can induce the release of pro-inflammatory cytokines (IL-1, IL-6 and TNF-α), followed by the hepatic stimulation of the acute phase response (APR). The inflammatory response of the host to these diseases can be more or less severe. The relationship between inflammatory response and metabolic changes is complex and not yet well understood. Therefore, 17 mid-lactating, non pregnant dairy cows were distributed into three experimental groups infused for 56 h: a hyperinsulinemic hypoglycemic clamp (HypoG, n=5) that provided an insulin infusion to achieve hypoglycemia (constant plasma hypoglycemia of 2.3 ± 0.01 mmol/l); a hyperinsulinemic euglycemic clamp (EuG, n=6) to study the effects of insulin; a control treatment (NaCl, n=6) with a 0.9% saline solution. Forthy eight hours after the start of the infusion, two udder quarters were challenged with 200 µg lipopolysaccharide (LPS) from E. coli. Blood was sampled before and 6.5 h after the LPS challenge and measured for plasma parameters related to metabolism and inflammatory response. Data were analyzed by the MIXED repeated procedure of SAS. At 6.5 h after the LPS challenge, plasma cholesterol level was decreased markedly in all groups, while albumin was decreased mainly in NaCl (P<0.05); plasma α-tocopherol (HypoG and NaCl), retinol (NaCl) and β-carotene (HypoG) were decreased (P<0.05). As to the positive acute phase reactants (+AP), however, a slight decline in plasma ceruloplasmin, particularly in NaCl group, was seen, instead the haptoglobin level showed no variation at this very short time after LPS. All the observed changes in the negative acute phase reactants (-AP) are typical of the very early acute phase response to which the increase of IL-6 and TNF-α could have contributed, particularly in EuG (P<0.01) and NaCl (P<0.05) groups. With respect to the effects of the metabolic situation, including those induced by infusion with insulin or insulin-glucose, few differences were observed. The HypoG animals (with the lowest glucose plasma levels) seem to respond less to inflammation (e.g. non significant variations of cytokines) than EuG and NaCl. In conclusion very early inflammation can be detected by the increase of IL-6 and TNF-a but also by the decrease of -AP. Hypoglycemia seems to reduce the inflammatory response to LPS while high insulin “per se” does not seem to affect it.