Proinflammatory effects of IL-10 during human endotoxemia

IL-10 is considered a potent antiinflammatory cytokine that strongly inhibi ts the production of proinflammatory cytokines. Recent studies have suggest ed that IL-10 also has immunostimulatory properties on CD4(+), CD8(+) T cel ls, and/or NK cells, resulting in increased TFN-gamma production. To determ ine the effect of IL-10 on IFN-gamma production and related inflammatory re sponses in humans, 16 healthy subjects received a bolus i.v. Injection of L PS (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, pa rticularly when administered after LPS, enhanced LPS-induced IFN-gamma rele ase, as well as the release of the IFN-gamma -dependent chemokines IFN-gamm a -inducible protein-10 and monokine induced by IFN-gamma, while inhibiting or not influencing the production of IFN-gamma -inducing cytokines, Pn add ition, IL-10 treatment enhanced activation of CTLs and NK cells after LPS i njection, as reflected by increased levels of soluble granzymes, These data indicate that high-dose IL-10 treatment in patients,vith inflammatory diso rders can be associated with undesired proinflammatory effects.