Fever and acute phase response induced in dwarf goats by endotoxin and bovine and human recombinant tumour necrosis factor alpha

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Abstract
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 colt (E. coli) derived human (r.HuTNF-α) and bovine TNF (r.BoTNF-α) 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 conipared with the changes seen after E. coli endotoxin (LPS) was administered (dose: 0.1 μg/kg i.v.). Following a single injection of 4 μg/kg of r-.BoTNF-α, shivering and biphasic febrile response were observed, accompanied by tachycardia, inhibition of rumen contractions, drop in plasma zinc and iron concentrations, lynipho-penia, and neutropenia Followed by neutrophilia. The i.v. administration of a single injection of 4 μg/kg r.HuTNF-α induced shivering and biphasic febrile responses, accompanied by anorexia and a similar drop in plasml trace metal concentrations when compared with r.BoTNF-α-treated goats. The TNF-α-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-a was significantly shorter than after LPS. Moreover, the r.BoTNF-α induced a longer lasting neutrophilic leucopenia, less neutrophilia, and a more persistent lymphopenia than after LPS injection. Neither r.BoTNF-α nor LPS caused severe haemo-concentration. Furthermore, no cross-tolerance between r.BoTNF-α and LPS could be demonstrated. We conclude that both r.BoTNF-α and r.HuTNF-α induce many of the physiologic, haemacologic and metabolic changes that characterize the acute phase response to LPS. The overlapping biological activities of r.-BoTNF-α, r.HuTNF-α and LPS in dwarf goats may indicate that both recombinant tumour necrosis factors have some homology with caprine TNF-α.