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

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.