DEVELOPMENT OF HYPERTHERMIA FOLLOWING INTRACEREBROVENTRICULAR ADMINISTRATION OF ENDOTOXIN IN THE RAT - EFFECT OF KININ B-1 AND B-2 RECEPTORANTAGONISTS

1 E. coli lipopolysaccharide (LPS) produced a dose-dependent (dose ran ge: 0.02-150 mu g) increase in rat core temperature that was maximal 6 h after intracerebroventricular (i.c.v.) administration. LPS (200 ng) increased core temperature by 1.0+/-0.2 degrees C, 6 h following admi nistration, as compared to vehicle-treated controls (-0.2+/-0.2 degree s C). 2 LPS-induced (200 ng) hyperthermia was prevented by co-administ ration of the bradykinin (BK) B-2 receptor antagonist, Hoe 140 (10 and 30 pmol, i.c.v.) or by indomethacin (10 nmol, i.c.v.). 3 Systemic adm inistration of Hoe 140 at doses up to 1 mu mol kg(-1), s.c., did not a ttenuate LPS-induced (200 ng, i.c.v.) hyperthernia. However, LPS hyper thermia was significantly reduced by systemic administration of indome thacin (1 mu mol kg(-1), i.v.). 4 Co-administration of the selective B -1 receptor antagonists, [des-Arg(9), Leu(8)]BK (0.1-1 nmol, i.c.v.) o r [des-Arg(10)] Hoe 140 (0.1-1 nmol, i.c.v.), did not prevent LPS-indu ced hyperthermia. 5 It is concluded that the development of hypertherm ia following central administration of endotoxin requires activation o f central, but not peripheral bradykinin B-2 receptors. The formation of kinins within the CNS may be an important initial component of CNS inflammation following infection.