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

Abstract

To determine whether a single injection of recombinant human interleukin-11 (rhIL-11) to human subjects would affect endotoxin-inducible cytokine production, 6 dialysis-dependent patients with renal failure and 4 healthy volunteers were subcutaneously injected with rhIL-11 (50 µg/kg). The circulating 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 dialysis-dependent patients. Venous blood obtained before and after rhIL-11 was stimulated with 10 ng/ml of LPS for 24 h at 37°C and production of TNFα, IL-1β, and IL-8 determined. The maximum suppression of IL-1β, TNFα and IL-8 production (66%, 24% and 58%, respectively) was observed 1 h after rhIL-11 administration. After 24 h, when circulating concentration of rhIL-11 had decreased to near pre-injection levels, LPS-induced TNFα and IL-1β production remained suppressed (56 ± 17%, P < 0.05; 46 ± 4.7, P<0.01, respectively) but returned to baseline at 48 h. These findings suggest that there is a therapeutic benefit of single doses of rhIL-11 in reducing LPS-induced IL-1β and TNFα production.