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

Department of Medicine, Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, Colorado, USA

Adrian J. Puren

Department of Medicine, Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, Colorado, USA

Giamila Fantuzzi

Department of Medicine, Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, Colorado, USA

Gary R. Hamner

Department of Medicine, Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, Colorado, USA

Ullrich S. Schwertschlag

Genetics Institute, Inc., Cambridge, Massachusetts, USA

John L. Ryan

Genetics Institute, Inc., Cambridge, Massachusetts, USA

Charles A. Dinarello

Department of Medicine, Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver, Colorado, USA

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 TNF, IL-1ß, and IL-8 determined. The maximum suppression of IL-1ß, TNF 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 TNF and IL-1ß 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-1ß and TNF production.

Journal of Endotoxin Research, Vol. 5, No. 4, 197-204 (1999)
DOI: 10.1177/09680519990050040601


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