Ghrelin modulates innate immune and ileal responses to lipopolysaccharide administration in weaned pigs

Nicole C. Burdick Sanchez ^1* Jeffery W Dailey ¹ Rand Broadway ¹ Emily M Davis ² Brooke M Bowen ³ Amy Petry ⁴ Michael A Ballou ² Kristin Hales ³ Jeffery A Carroll ¹

• ¹ Livestock Issues Research Unit, Agricultural Research Service (USDA), Lubbock, United States
• ² Department of Veterinary Sciences, Texas Tech University, Lubbock, United States
• ³ Department of Animal and Food Sciences, College of Agricultural Sciences & Natural Resources, Texas Tech University, Lubbock, Texas, United States
• ⁴ Division of Animal Sciences, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, Missouri, United States

Ghrelin is a hormone mainly produced in the stomach and is known to stimulate feed intake. Recent evidence suggests ghrelin may affect immunity. This study evaluated whether repeated ghrelin administration prior to and following an inflammatory challenge (lipopolysaccharide; LPS) would alter the innate immune response. Weaned pigs (n = 36; age 21 d) were housed in individual pens and were fitted with temperature loggers on d -7 and jugular vein catheters for serial blood collection on d -3. Based on body weight, pigs were separated into 2 treatments: 1) Ghrelin -administered human ghrelin (5 µg/kg BW i.v.) every 12 h from -48 to 36 h relative to LPS administration at 0 h; and 2) Control -administered a similar volume of saline and LPS. Blood samples were collected at various timepoints relative to LPS administration. At 48 h, pigs were humanely euthanized, and samples of the jejunum and ileum were collected for histology. Ghrelin pigs gained more weight (P = 0.04) and had greater ADG (P = 0.02) compared to Control pigs. There was a treatment × time interaction (P = 0.03) for Flank temperature in which Ghrelin pigs had greater body temperature at 0, 2, 4 and 48 h post-LPS administration. Neutrophil concentrations and the neutrophil:lymphocyte ratio were reduced (P ≤ 0.04) in Ghrelin compared with Control pigs. There was a treatment × time interaction (P = 0.03) for eosinophil concentration, in which Ghrelin pigs had reduced eosinophils compared to Control pigs at 0 and 36 h post-LPS administration. There was a treatment × time interaction for serum concentrations of TNF-α, IFN-γ, Granulocyte-Macrophage Colony-Stimulating Factor, and IL-4 (P ≤ 0.04), with greater concentrations observed in Ghrelin compared with Control pigs. In the ileum, Ghrelin pigs had greater villi length, and reduced villus blunting score, lacteal dilation score, and lamina propria eosinophil count compared to Control pigs (P ≤ 0.04). Data from this study suggests ghrelin may provide some protection against endotoxin-induced inflammation in the ileum, while increasing basal concentrations of cytokines. Further research is necessary to fully understand the impact of ghrelin on the inflammatory response in weaned pigs.