Non-therapeutic administration of antimicrobial growth promoters to interrogate suppression mechanisms of innate and adaptive immune responses using an ovine model of stress

Abstract

Abstract Antimicrobial growth promoters (AGPs) have been administered in non-therapeutic concentrations in livestock feed to increase weight gain per unit of feed consumed. Daily low-dose antibiotic administration is capable of modulating immunity by suppressing inflammation, potentially increasing metabolic resources that can be allocated to muscle development. It is unknown how the AGPs tylosin (TYL) and chlortetracycline (CTC) influence acquired immunity. The objective of this study was to measure acquired immune responses, assess impacts on innate immunity and to elucidate mechanisms of immunosuppression by immunizing 10-week old lambs (male Suffolk cross) with keyhole limpet hemocyanin (KLH) during AGP administration (TYL, CTC or Control diets) while enduring intermittent physical stress. Over a 4-week period, 18 lambs (n=3 per diet/stress group) were monitored. Between the third-fourth experimental week, stressed lambs gained less weight (1.50 ± 0.49 kg) than non-stressed lambs (3.06 ± 0.37 kg, P < 0.03). The weight of lambs fed AGPs did not surpass those on the control diet. Diet and stress did not impact serum concentrations of total IgG and IgM, or anti-KLH IgG and IgM specific titres. Endpoint hematological analysis revealed that stressed lambs had decreased red cell distribution width (RDW%, 29% vs. 31%, P<0.01) and peripheral lymphocyte populations (5.72 × 103/μL vs. 4.69 × 103/μL, P<0.02). A diet × stress interaction was observed for peripheral granulocyte population (P=0.02). The impending restriction of AGP usage in North America has generated interest in identifying AGP alternatives, and elucidation of the mechanisms of AGP function is needed to develop effective non-antibiotic alternatives that mimic their action.