Proinflammatory effects of IL-10 during human endotoxemia

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 TFN-gamma production. To determine the effect of IL-10 on IFN-gamma 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 mug/kg), administered just before or 1 h after LPS, IL-10 treatment, particularly when administered after LPS, enhanced LPS-induced IFN-gamma release, as well as the release of the IFN-gamma -dependent chemokines IFN-gamma -inducible protein-10 and monokine induced by IFN-gamma, while inhibiting or not influencing the production of IFN-gamma -inducing cytokines, Pn 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,vith inflammatory disorders can be associated with undesired proinflammatory effects.