Cytokines: Molecular keys to homeostasis, development, and pathophysiology

Identification and definition of the role and diversity of action of cytokines, the regulatory proteins including lymphokines, monokines, interleukins, interferons, and a variety of other growth factors produced by virtually every nucleated cell into the body and having pleiotropic regulatory effects on hematopoietic and many other cell types [Thompson, 1991], are in the forefront of biomedical research. The explosive development of cytokine research is reflected by the inclusion of “cytokine,” first introduced as a term in 1974 to recognize that lymphokines could be produced by other than lymphoid cells in 4,267 biomedical articles published by the end of 1992. From the initial reference to cytokines in 1974 to inclusion in 45 articles in 1985, the doubling of citations each succeeding year, together with 45% of all the citations since 1974 occurring in 1992 alone, attests to the continued rapid expansion of this area of biological research. The important roles of cytokines in many physiological processes and pathophysiological conditions, although largely descriptive in nature, were recognized during the early development of this field of investigation [Balkwill and Burke, 1989; Cohen et al., 1974]. Current and future directions, as highlighted by the series of Prospect articles featuring areas as diverse as embryologic, extracellular matrix, bone, hematologic, and neurologic development and function as well as in the organism's response to foreign organisms in this issue of the journal, are focused on broadening our understanding of the positive and negative influence of cytokines in normal and abnormal differentiation and development and on the molecular pathways underlying cytokine action. The broad areas of cellular biochemistry represented by the Prospects, moreover, emphasize the synthesis and convergence of cytokine research towards an understanding of the critical controls in development and homeostatsis.