Estimating glucose requirements of an activated immune system in growing pigs

Abstract

Activated immune cells become obligate glucose utilizers, and a large i.v. lipopolysaccharide (LPS) dose causes insulin resistance and severe hypoglycemia. Therefore, study objectives were to quantify the amount of glucose needed to maintain euglycemia following an endotoxin challenge as a proxy of leukocyte glucose requirements. Fifteen fasted crossbred gilts (30.3 ± 1.7 kg) were bilaterally jugular catheterized and assigned 1 of 2 i.v. bolus treatments: control (CON; 10 mL sterile saline; = 7) or LPS challenge + euglycemic clamp (LPS-Eu; 055:B5; 5 μg/kg BW; 50% dextrose infusion to maintain euglycemia; = 8). Following administration, blood glucose was determined every 10 min and dextrose infusion rates were adjusted in LPS-Eu pigs to maintain euglycemia for 8 h. Pigs were fasted for 8 h prior to the bolus and remained fasted throughout the challenge. Rectal temperature was increased in LPS-Eu pigs relative to CON pigs (39.8 vs. 38.8°C; < 0.01). Relative to the baseline, CON pigs had 20% decreased blood glucose from 300 to 480 min postbolus ( = 0.01) whereas circulating glucose content in LPS-Eu pigs did not differ ( = 0.96) from prebolus levels. A total of 116 ± 8 g of infused glucose was required to maintain euglycemia in LPS-Eu pigs. Relative to CON pigs, overall plasma insulin, blood urea nitrogen, β-hydroxybutrate, lactate, and LPS-binding protein were increased in LPS-Eu pigs (295, 108, 29, 133, and 13%, respectively; ≤ 0.04) whereas NEFA was decreased (66%; < 0.01). Neutrophils in LPS-Eu pigs were decreased 84% at 120 min postbolus and returned to CON levels by 480 min ( < 0.01). Overall, lymphocytes, monocytes, eosinophils, and basophils were decreased in LPS-Eu pigs relative to CON pigs (75, 87, 70, and 50%, respectively; ≤ 0.05). These alterations in metabolism and the large amount of glucose needed to maintain euglycemia indicate nutrient repartitioning away from growth toward the immune system. Glucose is an important fuel for the immune system, and data from this study established that the glucose requirements of an intensely and acutely activated immune system in growing pigs are approximately 1.1 g/kg BW/h.

Lipopolysaccharide immune stimulation but not β-mannanase supplementation affects maintenance energy requirements in young weaned pigs

“…During an immune challenge, pro-inflammatory cytokines initiate a shift in nutrient partitioning away from tissue growth to support activation and maintenance of an immune response [ 1 , 11 , 31 ]. The results of this experiment clearly demonstrated that a systemic inflammatory response to LPS occurred, verified by increased concentrations of pro-inflammatory cytokines and elevated body temperature.…”

“…Fever is an energetically expensive process and its effects on sheep and human maintenance energy requirements have been estimated [ 10 ]. Immune system activation also significantly shifts glucose metabolism and glucose requirements during an LPS challenge in pigs have been estimated to be approximately 1.1 g/(kg BW 0.75 ·h) [ 11 ]. Yet few studies have addressed comprehensive changes in energy partitioning during an immune response and clear relationships between measured immune responses and the direction and magnitude of changes in energy partitioning have yet to be elucidated.…”

Transition Period of the Dairy Cow Revisited: I. Homeorhesis and Its Changes by Selection and Management

“…Infection and partitioning: Evidence indicates that "immunostimulation" (infection, the author) homeorhetically alters systemic metabolism in a coordinated effort to meet the energetic demands of leukocytes (Horst et al, 2018). Glucose is obligatory for the energy metabolism of immune cells, and a shift to its metabolism occurs with a requirement of approximately 1 g glucose/kg BW 0.75 per hour after an LPS challenge (Horst et al, 2018) or of > 1 kg glucose within 720 min (Kvidera et al, 2017), an effect that will impair other functions.…”

Amino acid requirements of health challenged pigs

“…The immune system relies heavily on glucose to generate energy, and when the immune system becomes activated, several immune cell types rely on a metabolic switch favoring glycolysis rather than oxidative phosphorylation for ATP . This is evidenced by substantial increases in circulating lactate and glucose utilization in LPS challenged growing pigs (Kvidera et al, 2017). Further, Gln is essential for immune cell activation, can serve as a fuel substrate for immune cells, and is necessary for lymphocyte protein synthesis (Waithe et al, 1975;Calder, 1995;.…”