Decreased interleukin 1 production in aplastic anaemia

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Abstract
Summary. Interleukin 1 (IL-1) is an important regulator of immune system function. IL 1 also affects baematopoiesis in vitro: it causes release of colony stimulating factors from fibroblasts and endothelial cells and can directly act on primitive haeniatopoietic stem cells. We investigated IL 1 production in vitro by stimulated peripheral blood mononuclear cells of patients with aplastic anaemia (N = 17), patients with other haematologic diseases (N = 27), and normal individuals (N = 22) using a bioassay for IIL 1 activity. Ten aplastic patient s showed markedly decreased IL 1 production. IL 1 production by fibronectin-affinity purified monocytes was decreased in six of seven of these patients: in three other cases, in which IL 1 mononuclear cell production was undetectable, sufficient monocytes could not be isolated. IL lα and IL 1β precursor molecules were also absent or much decreased when mononuclear cell lysates from these patients were analysed by immunoblot using specific polyclonal sera. Aplastic patients with low IL 1 production were distinguished by the severity of their disease and the degree of neutropenia. Patients with rnyelodysplasia with comparable degrees of pancytopenia had normal IL 1 production. This is the first example of deficient haematopoietic growth factor production in a bone marrow failure syndrome. Decreased IL I production may contribute to the pathogenesis of some cases of aplastic anaemia and to susceptibility to infection.