To examine the role of interleukin-1 beta (IL-1 beta) in mediating sic
kness, we studied the effects of lipopolysaccharide (LPS) and IL-1 bet
a on social behavior in endotoxin-responsive C3H/HeOuJ (OuJ) mice and
endotoxin-resistant C3H/HeJ (HeJ) mice. Whereas LPS (1, 10 and 100 mu
g) depressed social behavior and body weight compared to saline in OuJ
mice, in HeJ mice it did not. To determine if the refractoriness of H
eJ mice to the behavioral effects of LPS was related to secretion of I
L-1 beta, in a second study, HeJ and OuJ mice were injected IP with LP
S (10 mu g) and plasma concentration of IL-1 beta was determined posti
njection. At 4 h postinjection, the plasma concentration of IL-1 beta
was increased by LPS in OuJ mice, but not in HeJ mice. The increase in
plasma IL-1 beta in OuJ mice corresponded to the maximal depression i
n social behavior. To further verify that HeJ mice are refractory to t
he behavioral effects of LPS because they fail to respond and produce
cytokines, the social behavior of HeJ and OuJ mice injected IP with re
combinant murine IL-1 beta (0, 50, 100, or 200 ng) was compared. As an
ticipated, exogenous IL-1 beta depressed social behavior similarly in
endotoxin-responsive OuJ mice and endotoxin-resistant HeJ mice. These
data indicate that a genetic mutation in HeJ mice that prevents LPS-in
duced synthesis of cytokines also renders HeJ mice refractory to the b
ehavioral effects of LPS. (C) 1997 Elsevier Science Inc.