PSIV-21 Time course and peak response of inflammation and tissue zinc transporters during LPS-induced sepsis in nursery pigs fed pharmacological levels of dietary zinc and copper

Abstract

Abstract This study evaluated the effects of lipopolysaccharide (LPS) injection on the immune response over a 24-h period in nursery pigs. Pigs consumed corn-soybean meal-based diets with added pharmacological levels of ZnO (d 0–14) and CuSO4 (d 14–23). On d 23, thirty pigs were randomly blocked based on BW and sex to one of five-time points (h 0 baseline, 3, 6, 12, and 24 post-challenge) and injected with a single i.m. LPS (O55:B5) at 12 μg/kg BW. At each time point, BW, rectal temperature (RT), and blood samples (n = 30, 24, 18, 12, and 6 per time point, respectively) were collected before one block (n = 6) was euthanized for liver and duodenum collection. Tissue samples were quantified for interleukin-6 (IL-6), zinc transporters (duodenal Zip4 and hepatic Zip14), and metallothionein-1 (MT-1) mRNA expression. Data were analyzed using PROC GLIMMIX of SAS with pig as the experimental unit. Following LPS, RT increased from h 0 to 6 (P < 0.05), and serum TNF-α increased from h 0 to 3 (P < 0.0001). Serum zinc and copper decreased (P < 0.01) from h 0 to 6, and h 0 to 12, respectively. Serum C-reactive protein tended to increase linearly following LPS (P = 0.10). LPS upregulated duodenal Zip4 and MT-1 (P < 0.05) at h 12 and 24, respectively, while all hepatic genes increased (P < 0.01) at h 3 post-challenge. Duodenal IL-6 did not change over time (P > 0.05). Quantification of mRNA expression displayed a positive correlation (P < 0.01) among hepatic IL-6, Zip14, and MT-1 in pairwise comparisons. In summary, LPS challenge induces fever and hepatic inflammation with consequent increases in hepatic and duodenal zinc importers, and their metal-binding protein, along with decreases in serum zinc and copper concentrations. However, our data indicate that pigs recover within 24-hour post-challenge.