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Interleukin-1 and interleukin-1 antagonism
CA Dinarello
Department of Medicine, Tufts University School of Medicine, Boston, MA.
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 the synthesis
of several proteins that, in turn, induce acute and chronic inflammatory
changes. IL-1 is also the prototypic "alarm" cytokine in that it brings
about increases in a variety of defense mechanisms, particularly
immunologic and hematologic responses. Most studies on the biology of IL-1
have been performed in animals, but human subjects have recently been
injected with recombinant IL-1 and the results confirm the two fundamental
properties of IL-1 as being both a mediator of disease as well as of host
defense. However, in either situation, over or continued production of IL-1
leads to debilitation of normal host functions; therefore, reduction of
IL-1 synthesis or its effects becomes a target of therapy in many diseases.
In this review, the structure, gene expression, synthesis, and secretion of
IL-1 are described. In addition, the two IL-1 surface receptors, possible
signal transduction mechanisms, various biologic activities, and production
of IL-1 during disease states are discussed. Similarities and differences
between IL-1, tumor necrosis factor, and IL-6 are presented. Although
various agents for reducing the synthesis and/or for antagonizing the
effects of IL-1 have been proposed, the recent cloning of a naturally
occurring IL-1 receptor antagonist (IL- 1ra) has opened new experimental
and clinical approaches. The ability of this IL-1ra to block the triggering
of IL-1 receptors in animals without agonist effects has reduced the
severity of diseases such as hemodynamic shock, lethal sepsis, inflammatory
bowel disease, experimental arthritis, and the spontaneous proliferation of
human leukemic cells.
Volume 77,
Issue 8,
pp. 1627-1652,
04/15/1991
Copyright © 1991 by The American Society of Hematology
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