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Infection and Immunity, March 2000, p. 1014-1018, Vol. 68, No. 3
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Reduced Th1, but Not Th2, Cytokine Production by Lymphocytes
after In Vivo Exposure of Healthy Subjects to Endotoxin
Fanny N.
Lauw,1,2,*
Tessa
ten Hove,1
Pascale E. P.
Dekkers,1
Evert
de
Jonge,3
Sander J. H.
van Deventer,1 and
Tom
van der
Poll1,2
Laboratory of Experimental Internal
Medicine,1 Department of Infectious Diseases,
Tropical Medicine, and AIDS,2 and Department
of Intensive Care Medicine,3 University of Amsterdam,
Amsterdam, The Netherlands
Received 24 May 1999/Returned for modification 29 September
1999/Accepted 1 December 1999
Endotoxin (lipopolysaccharide [LPS]) tolerance is characterized
by a reduced capacity of monocytes to produce proinflammatory cytokines upon restimulation in vitro. To determine whether LPS exposure induces a change in lymphocyte cytokine production and whether
this results in a shift in the T-helper 1 (Th1)/Th2 balance, whole blood obtained from seven healthy subjects before and after an
intravenous injection of LPS (4 ng/kg) was stimulated in vitro with
the T-cell stimulus anti-CD3/CD28 or staphylococcal enterotoxin B. Whole-blood production of the Th1 cytokines gamma interferon (IFN-
)
and interleukin-2 (IL-2) was markedly reduced at 3 and 6 h,
while the production of the Th2 cytokines IL-4 and IL-5 was not
influenced or was slightly increased. The IFN-
/IL-4 ratio was
strongly decreased at 6 h. Serum obtained after LPS exposure could slightly inhibit the release of IFN-
but increased
IL-4 production during stimulation of blood drawn from subjects not previously exposed to LPS. Normal serum also inhibited IFN-
production, albeit to a lesser extent. LPS exposure influences
lymphocyte cytokine production, resulting in a shift toward a Th2
cytokine response, an effect that may be mediated in part by soluble
factors present in serum after LPS administration in vivo.
*
Corresponding author. Mailing address: Laboratory of
Experimental Internal Medicine, Rm. G2-105, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam,
The Netherlands. Phone: 31-20-5666034. Fax: 31-20-6977192. E-mail: F.N.Lauw{at}AMC.UVA.NL.
Infection and Immunity, March 2000, p. 1014-1018, Vol. 68, No. 3
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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