Subcutaneous administration of recombinant glycosylated interleukin 6 in patients with cancer: Pharmacokinetics, pharmacodynamics and immunomodulatory effects

Rosamonde E. Banks*, Mary A. Forbes, Poulam M. Patel, Mark Storr, Susan Hallam, Deborah Clarke, Daniela Novick, Eileen Ingham, Christopher Bowmer, Jennifer Southgate, Ludwik K. Trejdosiewicz, John Illingworth, Timothy J. Perren, Peter J. Selby

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


This is the first report of the serum profile of a glycosylated recombinant form of human IL-6 (rhIL-6) administered subcutaneously (1-10 μg/kg/day) in a phase I/II trial as a thrombopoietic agent in patients with advanced cancer. The pharmacodynamic effects of IL-6 were also examined. Detailed pharmacokinetic measurements were made in four patients. Peak concentrations at 5-8 h and a median t0.5 of ca. 5 h were similar to those previously reported for non-glycosylated IL-6. However, higher peak concentrations and apparent differences in effective dose levels to those previously reported with the non-glycosylated form were seen. Indications of an apparent attenuation in circulating IL-6 concentrations with continuing injections were seen in eight of 10 patients examined but anti-IL-6 antibody generation was seen in only two patients. Soluble interleukin 6 receptor concentrations generally decreased. No major changes in T cell subsets were seen but expression of CD25 and CD54 by T lymphocytes significantly increased, accompanied by marked increases in soluble CD25 (sIL-2R) and CD54 (sICAM-1). No consistent change in B cells, monocytes or NK cells were seen. No evidence for induction of TNF-α was found. This study demonstrates similar biological effects of glycosylated rhIL-6 to those reported for the non-glycosylated form but illustrates several apparent differences which are discussed further. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)388-396
Number of pages9
Issue number4
Publication statusPublished - 1 Apr 2000


  • Clinical trial
  • Glycosylated
  • Immunomodulation
  • Interleukin 6
  • Pharmacokinetics

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