FEVER AND CHANGES IN PLASMA ZINC AND IRON CONCENTRATIONS IN THE GOAT - THE EFFECTS OF INTERFERON INDUCERS AND RECOMBINANT IFN-ALPHA-2A

Inflammation or invasion by pathogenic micro-organisms induces systemic changes, collectively known as the acute phase response. Among the varied alterations that together produce this response are fever, hypoferraemia and hypozincaemia. It is likely that these responses are mediated, in part, by production and release of cytokines such as interleukin-1 (II-1), interferons (IFN-α) and tumour necrosis factor (TNF). The present report describes a comparative study in dwarf goats on recombinant human IFN-α2a, (0·5 × l05 IU per kg intravenously (i.v.) and 0·5 × 106 IU per kg intramuscularly (i.m.)), Poly I:Poly C (an interferon inducer; 30 lag per kg i.v.), Newcastle disease virus La Sota strain (an interferon inducer; 0·5 ml per kg i.v.) and Escherichia coli endotoxin (an Il-1 and TNF induceri 0·1 lag per kg i.v.). The i.v. injection of recombinant IFN-α2a, caused characteristic monophasic febrile reactions, but no significant changes in plasma zinc and iron concentrations. The temperature responses were not due to endotoxin contamination because polymyxin B, which blocks endotoxin, had no inhibitory effect on the pyrogenicity of IFN-α2a. In contrast, the IFN-α2a-induced fever was completely prevented by flurbiprofen pretreatment (1 mg per kg i.v.). In contrast to the i.v. administration, i.m. injection of IFN-α2a, caused fever, hypoferraemia and hypozincaemia. Similar results were obtained after E. coli endotoxin, NCD La Sota strain and Poly I:Poly C injection. However, the shapes of the temperature curves and the changes in trace metal concentrations were markedly different. These data support the theory that fever and the changes in plasma zinc and iron concentrations are regulated by different mechanisms. © 1990 Academic Press Limited.