Elsevier

Cytokine

Volume 12, Issue 4, April 2000, Pages 388-396
Cytokine

Regular Article
SUBCUTANEOUS ADMINISTRATION OF RECOMBINANT GLYCOSYLATED INTERLEUKIN 6 IN PATIENTS WITH CANCER: PHARMACOKINETICS, PHARMACODYNAMICS AND IMMUNOMODULATORY EFFECTS

https://doi.org/10.1006/cyto.1999.0556Get rights and content

Abstract

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 t0.5of 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.

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    Correspondence to: Dr R. E. Banks, ICRF Cancer Medicine Research Unit, St James's University Hospital, Leeds LS9 7TF, UK

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