Reduced Th1, but not Th2, cytokine production by lymphocytes after in vivo exposure of healthy subjects to endotoxin.
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.
Lauw
F N
FN
Laboratory of Experimental Internal Medicine, University of Amsterdam, Amsterdam, The Netherlands. F.N.Lauw@AMC.UVA.NL
ten Hove
T
T
Dekkers
P E
PE
de Jonge
E
E
van Deventer
S J
SJ
van Der Poll
T
T
D000328:Adult; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000633:toxicity*; D018655:Lymphocyte Count / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018417:Th1 Cells / Q000502:physiology; D018418:Th2 Cells / Q000502:physiology
D016207:Cytokines; D007376:Interleukin-2; D015848:Interleukin-5; D008070:Lipopolysaccharides; D015847:Interleukin-4; D007371:Interferon-gamma