Local cytokine induction by lps in the rat air pouch and its
relationship to the febrile response.
Miller, Andrew J., Giamal N. Luheshi, Nancy J. Rothwell & Stephen
J. Hopkins.
School of Biological Sciences, 1.124, Stopford Building, University
of Manchester, Manchester, M13 9PT and University of Manchester
Rheumatic Disease Centre, Hope Hospital, Salford, M6 8HD, England
APStracts 3:0369R, 1996.
Peripheral induction of cytokines is a critical event in the induction
of febrile responses. The sequence of induction and site of action of
these cytokines, however, remains unclear. The objective of the
present study was to investigate the kinetics of local and systemic
production of interleukin(IL)-1, IL-6 and tumor necrosis factor
(TNF), with the aim of identifying the relationship between these
cytokines and the febrile response induced by injection of
lipopolysaccharide (LPS) into a subcutaneous air pouch in the rat.
Intrapouch injection of LPS induced dose-dependent fevers and
increases in the concentration of bioactive IL-6 in the plasma.
Further studies, using 100[mu]g/kg LPS, demonstrated significant
increases in local (air pouch) concentrations of bioactive IL-1, TNF
and IL-6, and circulating IL-6. No significant increases in TNF or
IL-1 were detected in the plasma of the same animals. Local TNF was
induced rapidly and peaked 1h after LPS injection. The kinetics of
local IL-1 and IL-6 induction were similar and both peaked after 3h.
The rise in local IL-6 preceded that of plasma IL-6 and reached a
peak concentration which was 25-fold higher than that observed in the
plasma. The data indicates that IL-1 and TNF act locally at the site
of inflammation and that locally induced IL-6 is the important
systemic mediator of the response.
Received 22 May 1996; accepted in final form 2 October 1996.
APS Manuscript Number R288-6.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996