ENDOTOXIN ELICITS NORMAL TRYPTOPHAN AND INDOLEAMINE RESPONSES BUT IMPAIRED CATECHOLAMINE AND PITUITARY-ADRENAL RESPONSES IN ENDOTOXIN-RESISTANT MICE

The neurochemical and endocrine responses to endotoxin (LPS), Newcastle disease virus (NDV) and interleukin-1 (IL-1) administration were studied in endotoxin-resistant mice. LPS has long been known to be a potent stimulator of the hypothalamo-pituitary-adrenocortical axis, but it also increases brain concentrations of the catabolites of norepinephrine (NE) and serotonin (5-HT), as well as free tryptophan. Mice of the endotoxin-resistant C3H/HeJ strain showed markedly reduced responses in plasma ACTH and corticosterone (CS) to intraperitoneal LPS compared to the control C3H/HeN strain. C3H/HeN mice displayed increases in the cerebral NE catabolite, MHPG, and the dopamine catabolite, DOPAC, but no such increases occurred in C3H/HeJ mice. However, the indolaminergic responses, increases of tryptophan and ther serotonin catabolite, 5-HIAA, were similar in the two strains. NDV administration induced responses very similar to those of LPS; increases in tryptophan and 5-HIAA, but impaired responses in catecholamines, ACTH and CS. IL-1 is known to be synthesized and secreted following LPS (and probably NDV) administration, and produces similar endocrine and neurochemical effects. IN C3H/HeJ mice, IL-1 elicited normal increases in plasma ACTH and CS, as well as cerebral MHPG, 5-HIAA and tryptophan. Thus the deficits in C3H/HeJ mice do not reflect alterations in the ability of catecholamines and the HPA axis to respond to the immune system, but probably occur early int eh sequence of reactions initiated by LPS and NDV. These results also suggest that LPS activates cerebral catecholamines and the HPA axis by similar or related mechanisms, whereas the indolaminergic responses apparently occur via a different mechanism.