Tolerance to lipopolysaccharide is related to the nitric oxide pathway

REPEATED administration of lipopolysaccharide (LPS) induces a refractory st ate to its usual pyrogenic effects which is called endotoxin tolerance. We tested the hypothesis that nitric oxide (NO) participates in the endotoxin tolerance. Single injection of LPS resulted in an-elevation in body tempera ture (T-b), whereas a significant reduction of the thermoregulatory respons e to LPS was:observed to repeated administration of LPS (administered at 48 h intervals). Intracerebroventricular (i.c.v.) injection of L-NAME (a non- selective NO inhibitor of nitric oxide synthesis) markedly enhanced the feb rile: response to LPS in tolerant rats. The data suggest;that NO pathway in the central nervous system plays a role in endotoxin tolerance. (C) 1999 L ippincott Williams & Wilkins.