IngentaConnect Modulatory in vitro effects of interleukin-1 receptor antagonist ...

Authors: Stošić-Grujičić, S.¹; Basara, N.²; Dinarello, C. A.³

Source: Clinical & Laboratory Haematology, Volume 21, Number 3, June 1999 , pp. 173-186(14)

Abstract:

We investigated the effects of interleukin-1 receptor antagonist (IL-1Ra) on the spontaneous proliferation and AML colony forming unit (CFU-AML) formation of bone marrow and peripheral blood cells in 50 acute myeloid leukaemia (AML) patients. Exposure to IL-1Ra (10 μg/ml) caused either decreased, unaltered or increased AML cell proliferation, as well as of CFU-AML colony formation, depending on the individual patient, but the inhibitory effects were dominant. To evaluate the involvement of IL-1β converting enzyme (ICE) in the autonomous AML cell growth, the effects of an antisense oligonucleotide on ICE were examined in 19 of these patients. In a majority of patients, antisense ICE suppressed both AML cell proliferation and CFU-AML although a stimulatory effect was sometimes evident. The proportion of AML patients with suppression obtained by antisense ICE was higher than with IL-1Ra, suggesting the involvement of additional ICE-dependent cytokine(s) in AML cell growth besides IL-1. The presence of IL-1Ra or antisense ICE also suppressed the endogenous IL-1β production of AML cells, at both the level of pro-IL-1β and mature IL-1β. Although inhibition by IL-1Ra or antisense ICE on growth parameters of AML cells in vitro prevailed, indicating the importance of IL-1 activity in autonomous AML cell growth, stimulatory effects on the cells of some patients suggest that AML is a heterogenous disorder regarding IL-1β regulation.

Keywords: Acute myeloid leukaemia; interleukin-1 receptor antagonist; interleukin-1; interleukin-1β converting enzyme; progenitors

Document Type: Research article

DOI: 10.1046/j.1365-2257.1999.00221.x

Affiliations: 1: Institute for Biological Research `Sinisa Stanković' and 2: Institute of Haematology, Clinical Centre of Serbia, Belgrade, Yugoslavia and 3: University of Colorado, Health Sciences Center, Denver, Colorado, USA

The full text electronic article is available for purchase. You will be able to download the full text electronic article after payment.

$50.16 plus tax Refund Policy

Modulatory in vitro effects of interleukin-1 receptor antagonist (IL-1Ra) or antisense oligonucleotide to interleukin-1β converting enzyme (ICE) on acute myeloid leukaemia (AML) cell growth