Endogenous modulators of tnf and il-1 response are under partial
control of tnf in baboon bacteremia.
Redl, H., Schlag G., Paul E., Bahrami S., Buurman W. A., Strieter R.
M., Kunkel S. L., Davies J. Foulkes R.
Ludwig Boltzmann Institute for Experimental and Clinical
Traumatology, Vienna, Austria; Department of Surgery,
Rijksuniversiteit Limburg, Maastricht, The Netherlands; Department of
Internal Medicine, University of Michigan, Ann Arbor, USA; Department
of Pathology, University of Michigan, Ann Arbor, USA; Biocon Research
(Pty) Ltd., Pretoria, South Africa: Celltech Therapeutics Ltd.,
Slough, United Kingdom
APStracts 3:0194R, 1996.
Tumor necrosis factor (TNF) and interleukin-1 (IL-1) are two cytokines
for which naturally occurring inhibitors have been identified. The
present study was undertaken to evaluate the extent to which
scavenging of TNF in bacteremia attenuates the plasma levels of IL-1
receptor antagonist (IL-1ra) and soluble TNF receptors (sTNFR). Ten
male baboons received 2 x 109 CFU/kg live E. coli over 2 hours and
were subjected to either placebo or anti-TNF antibody (anti-TNFab)
treatment (1 mg/kg CDP571, Celltech, UK) 2 hours before E. coli
infusion (observation time - 72 hours). IL-1ra (range 50 - 100 ng/ml)
and sTNFR (range 55 kDa: 20-25 ng/ml, 75 kDa: 30 - 35 ng/ml) release
was more sustained than that of IL-1 and TNF and was significantly
attenuated by anti-TNF treatment, as were the circulating levels of
IL-1, IL-8, and monocyte chemotactic peptide (MCP-1) in the anti
-TNFab group. We conclude that the increase in circulating natural
cytokine modulators observed in nonhuman primate bacteremia is under
the partial control of endogenous TNF since it was influenced by
anti-TNF pretreatment. This attenuation is comparable to the anti-TNF
effect on the chemokine MCP-1.
Received 31 July 1995; accepted in final form 6 May 1996.
APS Manuscript Number R475-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 June 96