Effect of bovine genotype on innate immune response of heifers to repeated lipopolysaccharide (LPS) administration

This pilot study provides a preliminary assessment of the impact of genotype on acute innate immune pro inflammatory, metabolic and endocrine responses to repeated lipopolysaccharide (LPS) administered to growing heifers. Heifers (n = 4/genotype) were from unselected (stable milk yield since 1964, UH) or contemporary (CH) Holstein cows that differed in milk yield (6200 vs 11,100 kg milk/305 d) or from contemporary Black Angus (CA) cows bred to contemporary Red Angus bulls. Heifers were challenged with iv administration of 0.5 mu g LPS/kg body weight on day 1 (Challenge 1) and d 5 (Challenge 2) of study to assess endotoxin tolerance. Plasma was collected at -1, -0.5, 0, 1, 2, 3, 4, 6, 8, and 24 h relative to each LPS administration. Rectal body temperature (BT) was measured before each blood sampling and at 5 and 7 h. Data were analyzed by repeated measures with sampling time as the repeated effect. Each genotype had at least one pro-inflammatory response that indicated it might have a more robust response than the other genotypes. The CH heifers had a greater TNF-alpha response, UH heifers had greater IL-6 and XO responses and CA heifers had greater BT and SAA response to LPS than the other genotypes. There was a genotype by time by interaction as cortisol peaked earlier in CH and UH than in CA heifers. Glucose response was less in CA and insulin response was greater in CH heifers. Endotoxin tolerance to LPS was evident as pro-inflammatory, cortisol, glucose and insulin responses were less during Challenge 2 than during Challenge 1. Differences among genotypes during Challenge 1 were eliminated during Challenge 2 except for the greater SAA response in CA heifers and indicate the potential for differential impacts of genotype on the development of endotoxin tolerance. Specific reasons for these effects of genotype are not clear from these data but the results support the hypothesis for differential innate immune signaling among these bovine genotypes.