Autoregulation of interleukin 1 production

Interleukin 1 (IL 1) alpha and beta are distinct cytokines with a common receptor on target cells. Both have been implicated in immunity, inflammation and connective tissue metabolism. Their production is stimulated by microbial products and also by other cytokines derived from accessory cells and lymphocytes. Following reports that IL 1 can stimulate its own production, we have tested the effects of recombinant IL 1 on the synthesis and release of IL 1 alpha and beta by human blood mononuclear cells (MNC). We confirmed that autoinduction occurs but report also the novel finding that this effect is very concentration dependent. At some concentrations within the range found in vivo, recombinant IL 1 not only failed to stimulate further IL 1 production but also inhibited the background level of synthesis in 20-h MNC cultures. The negative feedback appears unrelated to prostaglandin E2 and interferon-gamma levels and could not be reproduced by adding transforming growth factor beta. This previously unrecognized autoregulation may be relevant to clinical diseases associated with pathogenic over-production of IL 1.