Decreased interleukin 1 production in aplastic anaemia

Interleukin 1 (IL-1) is an important regulator of immune system function. IL 1 also affects haematopoiesis in vitro: it causes release of colony stimulating factors from fibroblasts and endothelial cells and can directly act on primitive haematopoietic 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 IL 1 activity. Ten aplastic patients 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 1 alpha and IL 1 beta 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 myelodysplasia 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 1 production may contribute to the pathogenesis of some cases of aplastic anaemia and to susceptibility to infection.