Role of interferons and other cytokines in the regulation of the immune response

Cytokines represent the major factors involved in the communication between T cells, macrophages and other immune cells in the course of an immune response to antigens and infectious agents. A number of studies on mouse and human T helper (Th) clones have recently provided extensive evidence for the existence of different activities exhibited by Th cells (called Th1 and Th2), which was apparently inferred from the profile of cytokine secretion. The Thl-type immune response is generally associated with IgG2a production and the development of cellular immunity, the Th2-type response with IgE production, eosinophils and mast cell production. This review focuses on the role of different cytokines produced by macrophages (especially interferons (IFNs), TNF-α, IL-10 and IL-12) or T cells (IFNs, IL-2, IL-4, IL-10, IL-13 and TGF-β) in macrophage-T cell interactions and the cytokine relevance in the differentiation of Th cells towards the Thl or Th2 type of immune response. Th1-derived cytokines (IFN-gamma, IL-2, TNF-α) favor macrophage activation, whereas the Th2 cytokines (IL-4, IL-10, IL-13) exhibit suppressive activities on macrophage functions. A key role in the differentiation towards the Th1-type response is now attributed to IL-12, a recently described cytokine produced mainly by macrophages. Its production can be upregulated by IFN-gamma and is inhibited by IL-10 and IL-4. All this emphasizes the importance of macrophage-cytokine interactions in determining the type of immune response. This article also aims to review recent data concerning the roles of IFNs α/β (type I) and IFN-gamma (type II) in the regulation of the immune response. While there is much information on the regulatory effects of IFN-gamma (also called “immune IFN”) on the immune response, little is so far known of the role of type I IFNs. These cytokines, originally described as simple antiviral substances, are now taken to be important regulators of the immune response. Recent data indicate that these molecules (especially IFNs-α) specifically promote the differentiation towards the Th1-type response. The stimulatory effects of IFN-α on the generation of the Th1-type response may be involved in its therapeutic effects in some human diseases, including early AIDS, hypereosinophilia and certain tumors. It is reasonable to assume that, with the increasing interaction between basic and clinical research, considerably more will be understood about how IFNs and other cytokines interact in the modulation of the immune response, and how this knowledge can be successfully translated into new and more selective therapeutic strategies against human diseases.