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Infection and Immunity, July 2000, p. 3965-3970, Vol. 68, No. 7
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Peptidoglycan and Lipoteichoic Acid from Staphylococcus
aureus Induce Tumor Necrosis Factor Alpha, Interleukin 6 (IL-6), and IL-10 Production in Both T Cells and Monocytes in a
Human Whole Blood Model
J. E.
Wang,1,*
P. F.
Jørgensen,1
M.
Almlöf,1,2
C.
Thiemermann,3
S. J.
Foster,4
A. O.
Aasen,1 and
R.
Solberg2
Institute for Surgical Research,
Rikshospitalet-National Hospital, N-0027 Oslo,1
and Department of Pharmacology, School of Pharmacy, University
of Oslo, N-0316 Oslo,2 Norway, and
William Harvey Research Institute, St. Bartholomew's
Hospital, Medical College, Charterhouse Square, London EC1M
6BQ,3 and Department of Molecular
Biology and Biotechnology, University of Sheffield,
Sheffield,4 United Kingdom
Received 27 January 2000/Returned for modification 25 March
2000/Accepted 23 April 2000
We have examined the ability of peptidoglycan (PepG) and
lipoteichoic acid (LTA) isolated from Staphylococcus aureus
to induce the release of tumor necrosis factor alpha (TNF-
),
interleukin-6 (IL-6), and IL-10 in whole human blood and identified the
cellular origins of these cytokines. Both PepG and LTA induced
transient increases in TNF-
and IL-10 in plasma, with peak values at
6 and 12 h, respectively. IL-6 values increased
throughout the experimental period (24 h). The TNF-
, IL-6, and IL-10
release induced by PepG and LTA was dose dependent. Only PepG was a
potent inducer of TNF-
secretion. After stimulation of whole blood
with PepG or LTA, very pure populations of monocytes (CD14 positive), T
cells (CD2 positive), B cells (CD19 positive), and granulocytes (CD15 positive) were isolated by immunomagnetic separation and analyzed by reverse transcription-PCR for mRNA transcripts encoding
TNF-
, IL-6, and IL-10. The TNF-
mRNA results were inconclusive.
In contrast, PepG induced IL-6 and IL-10 mRNA accumulation in both T
cells and monocytes. LTA, as well as lipopolysaccharide, induced IL-6 and IL-10 mRNA production in monocytes and possibly in T cells.
Whether granulocytes and B cells produce cytokines in response to
bacterial stimuli remains obscure. Blockade of the CD14 receptors with monoclonal antibodies (18D11) had no influence on the PepG-induced release of TNF-
but attenuated the LTA-induced release of the same
cytokine. In conclusion, our data indicate that circulating T cells and
monocytes contribute to cytokine production in sepsis caused by
gram-positive bacteria.
*
Corresponding author. Mailing address: Institute for
Surgical Research, Rikshospitalet-National Hospital, Sognsvannsveien 20, N-0027 Oslo, Norway. Phone: 47 23 07 35 20. Fax: 47 23 07 35 30. E-mail: jacob.wang{at}klinmed.uio.no.
Infection and Immunity, July 2000, p. 3965-3970, Vol. 68, No. 7
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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