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Biologic basis for interleukin-1 in disease
CA Dinarello
Department of Medicine, Tufts University, Boston, MA USA.
To understand the role of the proinflammatory cytokine interleukin-1 (IL-1)
in disease, investigators have studied how production of the different
members of the IL-1 family is controlled, the various biologic activities
of IL-1, the distinct and various functions of the IL-1 receptor (IL-1R)
family, and the complexity of intracellular signaling. Mice deficient in
IL-1Beta, IL-1Beta converting enzyme, and IL-1R type I have also been
studied. Humans have been injected with IL- 1 (either IL-1alpha or
IL-1beta) for enhancing bone marrow recovery and for cancer treatment. The
IL-1-specific receptor antagonist (IL-1Ra) has also been tested in clinical
trials. The topics discussed in this review include production and
activities of IL-1 and IL-1Ra molecules, the effects of IL-1 on gene
expression, functions of cell-bound and soluble IL-1 receptors, the
importance of the IL-1R accessory protein, newly discovered signal
transduction pathways, naturally occurring cytokines limiting IL-1
production or activity, the effects of blocking cyclooxygenase and nitric
oxide, and the outcomes of IL-1 and IL-1 Ra in human trials. Special
attention is paid to IL-1beta converting enzyme and programmed cell death.
The roles of IL-1 in hematopoiesis, leukemia, atherosclerosis, and growth
of solid tumors are also discussed. This is a lengthy review, with 586
citations chosen to illustrate specific areas of interest rather than a
compendium of references. At the end of each section, a short commentary
summarizes what the author considers established or controversial topics
linking the biology of IL-1 to mechanisms of disease.
Volume 87,
Issue 6,
pp. 2095-2147,
03/15/1996
Copyright © 1996 by The American Society of Hematology
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