Interleukin-1 receptor antagonist inhibits endotoxin fever and
systemic interleukin-6 induction in the rat.
Luheshi, Giamal, Andrew J. Miller, Saskia Brouwer, Michael J.
Dascombe; Nancy J. Rothwell & Stephen J. Hopkins.
School of Biological Sciences, 1.124, Stopford Building, University
of Manchester, Oxford Road, Manchester M13 9PT, UK, and University of
Manchester Rheumatic Diseases Centre, Hope Hospital, Salford, M6 8HD,
UK
APStracts 2:0137E, 1995.
Though a number of studies indicate that the pyrogenic activity of
lipopolysaccharide (LPS) and/or interleukin-1 (IL)-1 is mediated via
induction of IL-6, this has been questioned by recent evidence
demonstrating a dissociation between fever and circulating IL-6. The
present study re-examines this relationship using human recombinant
interleukin-1 receptor antagonist (IL-1ra). Injection of LPS
(100[mu]g/kg, ip) into rats induced fever (2.0 degrees C) that was
significantly inhibited (p<0.05) when IL-1ra (16mg/kg ip) was
given 1h and 2h after LPS. The rise in plasma IL-6 preceded the
febrile response by 1-1.5h and, although the concentrations of
bioactive IL-6 in plasma and cerebrospinal fluid (CSF) were not
reduced at 4h, at 2h plasma and CSF IL-6 bioactivity was inhibited by
80% and 70% respectively, following a single injection of IL-1ra
(16mg/kg ip). Intracerebroventricular (icv) injection of IL-1ra
(200[mu]g/rat) inhibited LPS fever but did not affect the plasma IL-6
bioactivity measured 2 or 4h after ip LPS. These data show that
peripheral IL-1 plays a part in the induction of both fever and the
rise in plasma IL-6 that precedes it, and that IL-1 within the brain
is also important in the induction of fever by LPS.
Received 23 February 1995; accepted in final form 14 June 1995.
APS Manuscript Number E85-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 11 July 1995.