Interleukin-1 is one factor which regulates autocrine production of GM-CSF by the blast cells of acute myeloblastic leukaemia.
The role of interleukin-1 (IL-1) as a regulator of the autonomous growth of the blast cells of acute myeloid leukaemia (AML) has been studied on samples isolated from 15 patients. In nine out of 10 patients with evidence of partial autonomous blast cell growth. IL-1 further stimulated cell growth in both suspension culture and in a clongenic assay. IL-1 also stimulated cell growth in two out of three cases with no evidence of autonomous growth whereas no additional stimulation was observed in two cases with totally autonomous growth. In blast cells stimulated by IL-1, synthesis of granulocyte-macrophage colony stimulating factor (GM-CSF) was increased and the proliferative response to IL-1 was inhibited by an antibody to GM-CSF. In all samples with evidence of autonomous growth, blast cell conditioned medium (BCCM) contained IL-1 activity (range 0.7-74.2 units ml) and a polyclonal antibody to IL-1 markedly inhibited autonomous growth in four samples. BCCM from three of these four samples contained GM-CSF, the synthesis of which was suppressed when BCCM was prepared in the presence of anti-IL-1. Our data suggests that endogenous IL-1 is an important factor in the regulation of the production of GM-CSF and hence of autonomous growth of AML blasts, but that other mechanisms regulating GM-CSF production may exist.
Bradbury
D
D
University Department of Haematology, City Hospital, Nottingham.
Rogers
S
S
Kozlowski
R
R
Bowen
G
G
Reilly
I A
IA
Russell
N H
NH
D002455:Cell Division; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000473:pathology; D011994:Recombinant Proteins / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000473:pathology
D007375:Interleukin-1; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor