The role of interleukin-1 in host responses to infectious diseases

The polypeptide cytokine interleukin-1 (IL-1) affects nearly every tissue and organ system. IL-1 is the prototype of the pro-inflammatory cytokines in that it induces the expression of a variety of genes and synthesis of several proteins which, in turn, induce acute and chronic inflammatory changes. Most studies on the biology of IL-1 have been carried out in animals, but human subjects have recently been injected with recombinant IL-1 and the results confirm IL-1 as being a mediator of disease as well as host defense. However, overproduction of IL-1 leads to debilitation of normal host functions; therefore, reduction of IL-1 synthesis or blockade of IL-1 activity becomes a target of therapy in many diseases. Agents for reducing the synthesis or antagonizing the effects of IL-1 have been sought, but the naturally occurring IL-1 receptor antagonist (IL-1Ra) has opened new experimental and clinical approaches. The ability of IL-1Ra to block IL-1 receptors without agonist activities has reduced the severity of diseases such as septic shock, lethal sepsis, inflammatory bowel disease, experimental arthritis, and the spontaneous proliferation of human leukemic cells.