C3H HEJ MICE ARE REFRACTORY TO LIPOPOLYSACCHARIDE IN THE BRAIN/

C3H/HeJ mice are refractory to lipolysaccharide (LPS) in the periphery , primarily because their macrophages do not respond to LPS and produc e pro-inflammatory cytokines such as interleukin-1 (IL-1). To determin e if they are also refractory to LPS in the brain, behavior of C3H/HeJ mice was compared to LPS sensitive C3H/HeOuJ mice following intracere broventricular (ICV) injection of LPS. Whereas ICV injection of LPS (3 -1000 ng/mouse) depressed social behavior, food motivation, object inv estigation and body weight in C3H/HeOuJ mice, C3H/HeJ mice were entire ly refractory to LPS in the brain. To determine if the refractoriness of C3H/HeJ mice could result from an inability to synthesize IL-1, rec ombinant murine IL-1 was injected ICV in both mouse strains. Central a dministration of IL-1 (1 or 2 ng/mouse) depressed social behavior and body weight similarly in both endotoxin-sensitive C3H/HeOuJ mice and e ndotoxin-resistant C3H/HeJ mice. That C3H/HeJ mice were refractory to the behavioral effects of central LPS, but not IL-1, suggests that mic roglia (and other cells in the brain) in C3H/HeJ mice have in common w ith peripheral macrophages, an inability to respond to LPS and produce cytokines. These data suggest a genetic basis for sickness behavior a nd demonstrate the utility of preventing central cytokine production i n manipulating LPS-induced sickness behavior. (C) 1997 Elsevier Scienc e B.V.