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Clinical Cancer Research, Vol 2, Issue 3 501-506, Copyright © 1996 by American Association for Cancer Research

ARTICLES

Induction of interleukin 1 receptor antagonist after interleukin 1 therapy in patients with cancer

WC Kopp, WJ Urba, HC Rager, WG Alvord, JJ Oppenheim, JW Smith 2nd and DL Longo
Clinical Services Program, Science Applications International Corp. Services, Inc., National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA.

The interleukin 1 receptor antagonist (IL-1ra) is a naturally occurring molecule that shares homology with IL-1alpha and IL-1beta and binds competitively to IL-1 receptors. Serum concentrations of IL-1ra were measured by ELISA in patients enrolled in Phase I clinical trials of IL-1alpha and IL-1beta given by 15-min infusion. Pretreatment levels of IL-1ra were <1500 (mean, 453 +/- 57) pg/ml. IL-1ra levels were increased in some patients within 1 h of completing the IL-1 infusion. By 2 h after infusion, serum levels of IL-1ra had increased dramatically, and they remained stable 4 h after infusion. There was evidence that peak IL-1ra levels were IL-1 dose dependent. Seven patients treated with IL-1alpha had IL-1ra levels that exceeded 1 microgram/ml. In contrast, serum levels of IL-1 declined rapidly and were undetectable 1 h after completing IL-1 infusion in most patients receiving <1.0 microgram/kg. IL-1ra levels remained slightly elevated over pretreatment values in serum obtained 18-24 h after IL-1 infusion, but there was no evidence for progressive accumulation over repeated days of therapy. A similar pattern of IL-1ra elevation was observed after the last IL-1 infusion on day 6. This study shows that cancer patients produce 2 to >6 log incremental increases in IL-1ra rapidly following treatment with IL-1, a response that has implications for the design of future clinical trials with IL-1 and with agents thought to induce IL-1 production.


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[Abstract] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
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Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1996 by the American Association for Cancer Research.