Interleukin-1 and hematopoiesis

Abstract

Interleukin-1 alpha and interleukin-1 beta are 17.5 kDa peptides which exert a wide variety of biological activities. Both forms of interleukin bind to a common 60-70 kDa receptor expressed by most somatic cells. One major effect of interleukin-1 is to induce the expression of other genes, including genes for other interleukins (IL-6), colony stimulating factors (GM-CSF and G-CSF) and growth factors (PDGFA) and adhesion proteins (ELAM-1, ICAM-1). In vitro, cells of the hematopoietic stroma including thymic epithelium, endothelial cells, fibroblasts, T-lymphocytes, and macrophages, are all capable of responding to interleukin-1 by expressing most of these IL-1 inducible genes. Accordingly, because interleukin-1 has no direct effect on hematopoietic progenitor cells, its major effect on hematopoiesis is to regulate the expression of hematopoietic growth factor genes by other cells. The mechanism by which interleukin-1 induces gene expression is to first induce mRNA accumulation which accounts for an increase in translation of the mRNA. The accumulation of RNA, interestingly, does not result from increased transcription of these genes but by the stabilization of the mRNA. Ordinarily, the hematopoietic growth factor gene transcripts have a very short half-life but in an interleukin-1 induced cell, the half-life of these transcripts is markedly prolonged (greater than 24 h). This particular effect of IL-1 on transcript stability likely accounts for virtually all of the hematopoietic activities of interleukin-1 including: (1) induction of growth factors; (2) synergy with other factors; (3) priming; and (4) auto-induction. Three clinical models of hematopoiesis are presented which suggest that the interleukin-1 CSF network is operative in vivo. The ability of interleukin-1 to induce the expression of hematopoietic growth factor genes as well as genes whose products regulate cellular function and traffic suggest that interleukin-1 is an essential molecular master switch for a number of cellular responses occurring in organisms facing the vicissitudes of their environment.