Effects of polymyxin B on clinical signs, serum TNF-a, haptoglobin and plasma lactate concentrations in experimental endotoxaemia in sheep

Abstract

Introduction: The experiment evaluated the effects of intravenous administration of polymyxin B on experimental endotoxaemia in sheep. Material and Methods: Twenty clinically healthy fat-tailed sheep were randomly divided into: a group treated with 6,000 U/kg of polymyxin B, a group at 12,000 U/kg, and positive and negative controls. Endotoxaemia was induced by intravenous administration of lipopolysaccharide (LPS) from E. coli serotype O55:B5 at 0.5 µg/kg. polymyxin was infused intravenously along with 2.5 L of isotonic intravenous fluids at 20 mL/kg/h. The positive control group received LPS and 2.5 L of isotonic fluids, the negatives receiving just 2.5 L of isotonic fluids. Clinical signs were evaluated before and at 1.5, 3, 4.5, 6, 24, and 48 h after LPS administration. Blood was also sampled at the denoted hours and serum haptoglobin, tumour necrosis factor-a (TNF-a), and plasma lactate concentrations were assayed. Results: The serum concentration of TNF-a in the positive control group increased significantly up to 48 h after LPS administration. The concentration of TNF-a was significantly different from those of the polymyxin B and positive control groups from 3 to 48 h; also, the concentrations of haptoglobin at different times in the polymyxin groups were lower than those of the positive control group and were significant at hours 3 to 48 (P < 0.05). Following the LPS administration, haptoglobin and TNF-a concentrations changed without significant difference between the two polymyxin B groups. Conclusion: Polymyxin B (6,000 U/kg) restrained blood lactate concentrations. Furthermore, it significantly improved the clinical signs in endotoxaemic animals, including rectal temperature and heart and respiratory rates. Polymyxin B may be an antiendotoxic in fat-tailed sheep.