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Departments of
*
Experimental Internal Medicine and
Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
Department of Pathophysiology of Plasma Proteins, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam, The Netherlands; and
§
Fujisaki Institute, Hayashibara Biochemical Laboratories, Okayama, Japan
IL-10 is considered a potent antiinflammatory cytokine that
strongly inhibits the production of proinflammatory cytokines. Recent
studies have suggested that IL-10 also has immunostimulatory properties
on CD4+, CD8+ T cells, and/or NK cells,
resulting in increased IFN-
production. To determine the effect of
IL-10 on IFN- production and related inflammatory responses in
humans, 16 healthy subjects received a bolus i.v. injection of LPS (4
ng/kg) in combination with either placebo or recombinant human IL-10
(25 µg/kg), administered just before or 1 h after LPS. IL-10
treatment, particularly when administered after LPS, enhanced
LPS-induced IFN- release, as well as the release of the
IFN--dependent chemokines IFN--inducible protein-10 and monokine
induced by IFN-, while inhibiting or not influencing the production
of IFN--inducing cytokines. In addition, IL-10 treatment enhanced
activation of CTLs and NK cells after LPS injection, as reflected by
increased levels of soluble granzymes. These data indicate that
high-dose IL-10 treatment in patients with inflammatory disorders can
be associated with undesired proinflammatory
effects.
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