Transforming growth factor beta and interleukin-1: a paradigm for opposing regulation of haemopoiesis

Baillieres Clin Haematol. 1992 Jul;5(3):703-21. doi: 10.1016/s0950-3536(11)80013-2.

Abstract

The polypeptide cytokines, IL-1 and TGF-beta affect nearly every tissue and cell type in the body. IL-1 is the prototype of the proinflammatory molecule while TGF-beta is essentially anti-inflammatory. IL-1 is part of the cascade of cytokines that are produced during microbial invasion or bodily injury and enhance a variety of host responses, particularly in the immunological and haemopoietic systems, while TGF-beta acts as an inhibitor of these responses. At several levels, IL-1 and TGF-beta act in opposition to one another. IL-1 stimulates the expression of many genes in lymphoid and marrow stromal cells that stimulate haemopoietic cell growth and differentiation, while TGF-beta inhibits these IL-1 mediated effects. Also, TGF-beta stimulates secretion of the IL-1Ra. In addition, IL-1 induces the cell surface expression of cytokine receptors on lymphoid and haemopoietic cells, while TGF-beta dramatically inhibits the cell surface expression of these receptors, including the IL-1 receptor. Finally, IL-1 augments lymphoid and haemopoietic cell growth and TGF-beta potently inhibits this proliferation. The interactions of these cytokines serve to illustrate that the net balance of stimulatory and inhibitory signals determines the fate of a given cell which may be responsible for regulating homeostatic cell growth (Figure 1). Thus, the regulation of cytokine production and/or antagonism of their effects continues to be a therapeutic goal in the treatment of many diseases.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Bone Marrow Cells
  • Cell Cycle / drug effects
  • Cell Differentiation / drug effects
  • Cell Division / drug effects
  • Colony-Forming Units Assay
  • Cytokines / physiology
  • Gene Expression Regulation / drug effects
  • Hematopoiesis / physiology*
  • Hematopoietic Cell Growth Factors / physiology
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects
  • Humans
  • Interleukin-1 / pharmacology
  • Interleukin-1 / physiology*
  • Leukemia / pathology
  • Lymphocyte Activation / drug effects
  • Lymphoma / pathology
  • Mice
  • Models, Biological
  • Organ Culture Techniques
  • Receptors, Cell Surface / drug effects
  • Receptors, Cell Surface / physiology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • Transforming Growth Factor beta / pharmacology
  • Transforming Growth Factor beta / physiology*

Substances

  • Cytokines
  • Hematopoietic Cell Growth Factors
  • Interleukin-1
  • Receptors, Cell Surface
  • Transforming Growth Factor beta