Development: nature and nurture: Development – Genetics, Epigenetics and Environmental Regulation

Abstract

The Cytokine Network edited by Fran Balkwill Frontiers in Molecular Biology Series (seried editors B. D. Hames and D. M. Glover) Oxford University Press (2000) pp. 199. ISBN 019–963-702-4. 29.95 Cytokines are small- to medium-sized proteins and glycoproteins that mediate highly potent biological effects on many cell types. They have critical roles in haematopoiesis, inflammatory responses and the development and maintenance of immune responses. Importantly, cytokines act in networks or cascades. Typical properties of cytokines in these networks are pleiotropy, redundancy, synergistic activity and antagonistic effects upon each other. Knowledge of how these networks are comprised and operate is important in understanding how cytokines mediate their diverse effects on biological systems. In The Cytokine Network, Fran Balkwill brings together some distinguished investigators to produce a survey, in eight independently written and concise chapters, of the complex cytokine and chemokine (chemotactic cytokine) networks present in mouse and man. The ever-increasing complexity of cytokine networks is introduced in the initial chapter with a summary of the bioinformatics approach for the high throughput discovery of novel cytokines and chemokines. The burgeoning number of newly identified chemokines, chemokine receptors and TNF family members reminds us that our understanding of the cytokine network is extremely dynamic and that our interpretation of some pathways will change with the characterisation of new factors. The following chapters address the interactions of the cytokines, both with reference to their signalling pathways (well summarised in chapter 2) and their biological roles. The point is made that cytokines should be studied as a network rather than individually and that in vivo models, including the generation of transgenic and gene knock-out mice, are powerful tools for doing so. Rheumatoid arthritis is presented as a well-studied example of how inappropriate regulation of pro- and anti-inflammatory cytokines mediates autoimmune disease, and examples of immunoregulatory cytokines that have both overlapping and independent regulatory effects on inflammation are demonstrated within this context. The important Th1/Th2 paradigm receives a dedicated chapter. T helper type 1 and T helper type 2 cells produce distinct and restricted patterns of cytokines that cross regulate each other and thus mediate different types of immune response. The development of these subsets of T helper cells from a common precursor, as part of a developing immune response, has important effects on the cytokine network. The mechanisms of Th1/Th2 development together with modulating factors and associated intracellular signalling are well described. The chapter summarises well the role of Th1/Th2 development in human diseases with reference to transplantation immunology, neonatal development, autoimmune diseases, and atopic diseases. A very interesting review of the relationships between cytokines and viruses is given. Cytokines are critically involved in mediating antiviral immune responses. However, homologues of cytokines, chemokines and their receptors, after being ‘hijacked’ from the host genome and undergoing evolution along with the viral genes, are utilised by viruses themselves to promote their replication and to suppress immune responses against them. The chapter describes several noteworthy examples of these virally encoded cytokines and receptors together with their roles in vivo. This is a well-written book that provides a good introduction to understanding how cytokines and chemokines interact as a network in the immune system. The volume links together diverse subjects that include cytokine signalling, genomic polymorphism, disease processes and immunotherapies. The book does not aim to describe comprehensively the biology of all the currently known cytokines and chemokines and therefore alternative texts should be considered for this. (ABSTRACT TRUNCATED)