Effects of pentoxifylline and polymyxin B on the acute-phase-response to Escherichia coli endotoxin in dwarf goats.
The purpose of this study was to assess whether polymyxin B together with pentoxifylline, had beneficial effects on the acute-phase-response to E. coli endotoxin in the dwarf goat (n = 6). Polymyxin B partly neutralizes E. coli endotoxin by forming inactive polymyxin B-lipopolysaccharide (LPS) complexes; pentoxifylline has been reported to suppress the LPS-induced production of tumour necrosis factor (TNF-alpha). E. coli LPS (0.0067 microgram/kg/min over 30 min) induced fever, tachycardia, inhibition of rumen motility, a decline in WBC, lymphopenia, and decreases in plasma zinc and iron concentrations. Most of the haematological, blood biochemical and clinical effects of E. coli LPS were significantly reduced by polymyxin B pretreatment (0.1 mg/kg/min over 30 min, i.v.). Pentoxifylline (0.3 mg/kg/min over 30 min, i.v.) did not reduce the clinical and blood biochemical effects of E. coli LPS, however, it modulated the number of circulating neutrophils. No synergistic effects were observed after i.v. infusion of polymyxin B with pentoxifylline. The lack of synergy may be due to the production and release of pro-inflammatory cytokines other than TNF-alpha.
van Miert
A S
AS
Department of Veterinary Basic Sciences, Faculty of Veterinary Medicine, Utrecht University, The Netherlands.
van Duin
C T
CT
Wensing
T
T
D000210:Acute-Phase Reaction / Q000139:chemically induced / Q000662:veterinary*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001774:Blood Chemical Analysis / Q000662:veterinary; D001831:Body Temperature / Q000187:drug effects; D002452:Cell Count / Q000187:drug effects / Q000662:veterinary; D004731:Endotoxins / Q000008:administration & dosage / Q000633:toxicity*; D004926:Escherichia coli / Q000378:metabolism*; D005260:Female; D005334:Fever / Q000139:chemically induced / Q000662:veterinary; D005769:Gastrointestinal Motility / Q000187:drug effects; D006041:Goats; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous / Q000662:veterinary; D007501:Iron / Q000097:blood; D007962:Leukocytes / Q000187:drug effects; D008070:Lipopolysaccharides / Q000378:metabolism / Q000633:toxicity; D008231:Lymphopenia / Q000139:chemically induced; D008297:Male; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D010431:Pentoxifylline / Q000008:administration & dosage / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011112:Polymyxin B / Q000008:administration & dosage / Q000494:pharmacology*; D013610:Tachycardia / Q000139:chemically induced / Q000662:veterinary; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015032:Zinc / Q000097:blood
D000900:Anti-Bacterial Agents; D004731:Endotoxins; D008070:Lipopolysaccharides; D010726:Phosphodiesterase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D007501:Iron; D011112:Polymyxin B; D015032:Zinc; D010431:Pentoxifylline