167 Modulation of the Innate Immune Response to Lipopolysaccharide Through Ghrelin Administration in Weaned Pigs

Abstract

Abstract Ghrelin is a hormone produced in the gastrointestinal tract that is known to stimulate feed intake. However, recent evidence suggests ghrelin may have a role in inflammation reduction. Therefore, this study was designed to determine whether repeated ghrelin administration before and following an inflammatory challenge would alter the innate immune response. Weaned pigs (n = 36; 21 d of age) were transported to the Swine Building of the Livestock Issues Research Unit where they were housed in individual pens in an environmentally controlled room. Pigs had ad libitum access to water and a starter ration. On d -7 (3 days post arrival), pigs were fitted with temperature loggers within the intraperitoneal cavity (IP) or subcutaneously between the abdomen and the hind leg (Flank). On d -3, pigs were fitted with jugular vein catheters to allow for serial blood collection. Pigs were balanced by body weight measured following cannulation and assigned to 1 of 2 treatments: 1) Ghrelin: administered human ghrelin (5 µg/kg BW iv) every 12 h from -48 to 36 h relative to LPS administration at 0 h; 2) Control: administered saline at previously mentioned time points. Blood samples were collected at -48, -36, -24, -12, -2, -1, 0, 1 2, 3, 4, 5, 6,2, 24, 36 and 48 h relative to LPS administration. After collection of the 48-h sample, pigs were humanely euthanized, and samples of the jejunum and ileum were collected for histology. Pigs administered ghrelin gained more body weight (P = 0.04) compared with Control pigs after initiation of ghrelin administration. There was a treatment × time interaction (P = 0.03) for Flank temperature where Ghrelin pigs had greater body temperature at 0, 2, 4 and 48 h post-LPS challenge. Neutrophil and basophil concentrations and the neutrophil:lymphocyte ratio were reduced (P ≤ 0.04) in Ghrelin pigs compared with Control pigs. Additionally, there was a treatment × time interaction for eosinophil concentration (P = 0.03), where concentrations were reduced in Ghrelin pigs compared with Control pigs at 0 and 36 h post-LPS challenge. There were treatment × time interactions for serum concentrations of tumor necrosis factor-alpha, Interferon-gamma, granulocyte-macrophage-colony stimulating factor, and Interleukin-4 (P ≤ 0.04), with greater concentrations observed in Ghrelin compared with Control pigs. However, there was no effect of ghrelin administration on cortisol concentrations (P = 0.38). In the ileum, Ghrelin pigs had greater villi length, and reduced villus blunting score, lacteal dilation score, and lamina propria eosinophil count compared with 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.