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), Newcastl e disease virus (NDV) and interleukin-1 (IL-1) administration were stu died in endotoxin-resistant mice. LPS has long been known to be a pote nt stimulator of the hypothalamo-pituitary-adrenocortical axis, but it also increases brain concentrations of the catabolites of norepinephr ine (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 th e cerebral NE catabolite, MHPG, and the dopamine catabolite, DOPAC, bu t no such increases occurred in C3H/HeJ mice. However, the indolaminer gic responses, increases of tryptophan and ther serotonin catabolite, 5-HIAA, were similar in the two strains. NDV administration induced re sponses very similar to those of LPS; increases in tryptophan and 5-HI AA, but impaired responses in catecholamines, ACTH and CS. IL-1 is kno wn to be synthesized and secreted following LPS (and probably NDV) adm inistration, 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 i n C3H/HeJ mice do not reflect alterations in the ability of catecholam ines and the HPA axis to respond to the immune system, but probably oc cur early int eh sequence of reactions initiated by LPS and NDV. These results also suggest that LPS activates cerebral catecholamines and t he HPA axis by similar or related mechanisms, whereas the indolaminerg ic responses apparently occur via a different mechanism.