Fever and acute phase response induced in dwarf goats by endotoxin and bovine and human recombinant tumour necrosis factor alpha
Autor: | A. S. J. P. A. M. Miekt, Th. Wensing, C. T. M. Duin |
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Rok vydání: | 1992 |
Předmět: |
Male
medicine.medical_specialty Necrosis Fever Anorexia Biology Neutropenia law.invention Body Temperature Eating law Internal medicine medicine Animals Humans Castration Acute-Phase Reaction Pharmacology Goat Diseases General Veterinary Tumor Necrosis Factor-alpha Goats Acute-phase protein Hemodynamics medicine.disease Neutrophilia Recombinant Proteins Endotoxins Endocrinology Immunology Injections Intravenous Recombinant DNA Shivering Tumor necrosis factor alpha Cattle Female medicine.symptom |
Zdroj: | Journal of veterinary pharmacology and therapeutics. 15(4) |
ISSN: | 0140-7783 |
Popis: | Tumour necrosis factor (TNF), a polypeptide produced by mononuclear phagocytes, has been implicated as an important mediator of inflammatory processes and of clinical manifestations in acute infectious diseases. To study further the potential role of TNF in infectious diseases, recombinant Escherichia coli (E. coli) derived human (r.HuTNF-alpha) and bovine TNF (r.BoTNF-alpha) were intravenously (i.v.) administered in dwarf goats. Rectal temperature, heart rate, rumen motility, plasma zinc and iron concentrations, and certain other blood biochemical and haematological values were studied and compared with the changes seen after E. coli endotoxin (LPS) was administered (dose: 0.1 microgram/kg i.v.). Following a single injection of 4 micrograms/kg of r.BoTNF-alpha, shivering and biphasic febrile response were observed, accompanied by tachycardia, inhibition of rumen contractions, drop in plasma zinc and iron concentrations, lymphopenia, and neutropenia followed by neutrophilia. The i.v. administration of a single injection of 4 micrograms/kg r.HuTNF-alpha induced shivering and biphasic febrile responses, accompanied by anorexia and a similar drop in plasma trace metal concentrations when compared with r.BoTNF-alpha-treated goats. The TNF-alpha-induced symptoms were essentially the same as those that occurred after LPS administration. However, the time of onset of these changes after the injection of TNF-alpha was significantly shorter than after LPS. Moreover, the r.BoTNF-alpha induced a longer lasting neutrophilic leucopenia, less neutrophilia, and a more persistent lymphopenia than after LPS injection. Neither r.BoTNF-alpha nor LPS caused severe haemo-concentration. Furthermore, no cross-tolerance between r.BoTNF-alpha and LPS could be demonstrated. We conclude that both r.BoTNF-alpha and r.HuTNF-alpha induce many of the physiologic, haematologic and metabolic changes that characterize the acute phase response to LPS. The overlapping biological activities of r.BoTNF-alpha, r.HuTNF-alpha and LPS in dwarf goats may indicate that both recombinant tumour necrosis factors have some homology with caprine TNF-alpha. |
Databáze: | OpenAIRE |
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