NEUROCHEMICAL AND NEUROENDOCRINE RESPONSES TO NEWCASTLE-DISEASE VIRUS ADMINISTRATION IN MICE

Mice injected intraperitoneally with Newcastle disease virus (NDV) responded with increased plasma concentrations of ACTH and corticosterone and increased hypothalamic concentrations of the tryptophan and of the norepinephrine catabolite, 3-methoxy,4-hydroxyphenylethyleneglycol (MHPG) and the serotonin catabolite, 5-hydroxyindoleacetic acid (5-HIAA). Two different strains of NDV, a lentogenic and a mesogenic one, elicited dose-dependent effects in these responses. Both strains elicited near maximal responses at doses around 1000 hemagglutination units. The maximal effects on ACTH, corticosterone and MHPG occurred around 2 h, but the effects on tryptophan and 5-HIAA were greatest at 8 h. Similar responses in plasma corticosterone, and cerebral tryptophan and 5-HIAA were observed following i.p. injection of polyinosinic-polycytidylic acid, but MHPG was not altered. The cyclo-oxygenase inhibitor, indomethacin, had little effect on the NDV-induced increases in plasma corticosterone and ACTH, and hypothalamic indolamines, but essentially ablated the MHPG response. The effect of NDV on plasma corticosterone, like that of endotoxin (LPS), was prevented by hypophysectomy, suggesting that the pituitary was required for these responses. These endocrine and neurochemical responses to NDV resemble those to interleukin-l (IL-1) and LPS. Therefore we tested mice pretreated with the IL-l-receptor antagonist. This treatment prevented the neurochemical and plasma ACTH and corticosterone responses to IL-1, but did not alter those to LPS, and prevented the endocrine and neurochemical responses to NDV in approximately half of the animals. Thus IL-1 may be a mediator of the responses to NDV, but additional factors may also be involved.