Suppression of endotoxin-inducible cytokines in whole blood from human subjects following single dose of recombinant human interleukin-11

To determine whether a single injection of recombinant human interleukin-11 (rhIL-11) to human subjects would affect endotoxin-inducible cytokine prod uction, 6 dialysis-dependent patients with renal failure and 4 healthy volu nteers were subcutaneously injected with rhIL-11 (50 mu g/kg). The circulat ing concentrations of rhIl-11 remained at a constant level of approximately 12 ng/ml for 0.25-6 h in healthy volunteers but were 2-fold higher in dial ysis-dependent patients. Venous blood obtained before and after rhIL-11 was stimulated with 10 ng/ml of LPS for 24 h at 37 degrees C and production of TNF alpha, IL-1 beta, and IL-8 determined. The maximum suppression of IL-1 beta, TNF alpha and IL-8 production (66%, 24% and 58%, respectively) was o bserved 1 h after rhIL-11 administration. After 24 h, when circulating conc entration of rhIL-11 had decreased to near pre-injection levels, LPS-induce d TNF alpha and IL-1 beta production remained suppressed (56 +/- 17%, P < 0 .05; 46 +/- 4.7, P<0.01, respectively) but returned to baseline at 48 h. Th ese findings suggest that there is a therapeutic benefit of single doses of rhIL-11 in reducing LPS-induced IL-1 beta and TNF alpha production.