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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-gamma ) 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-gamma /IL-4 ratio was strongly decreased at 6 h. Serum obtained after LPS exposure could slightly inhibit the release of IFN-gamma but increased IL-4 production during stimulation of blood drawn from subjects not previously exposed to LPS. Normal serum also inhibited IFN-gamma 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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