Cytokines and macrophages: implications for normal and abnormal renal development.
Work with transgenic animals and in vitro manipulation of organs in culture has highlighted an increasing number of genes that are important in the normal development of the kidney and whose disruption inhibits nephrogenesis. The phenotype seen with some agents resembles that of the congenital renal anomaly renal dysplasia, in which there appears to be an arrest of normal development. Such molecules include inflammatory cytokines, factors that have traditionally been described as intercellular messengers in the immune system. Although the mechanisms of action of cytokines in organogenesis have not yet been fully delineated, these may include alterations in normal expression patterns of adhesion molecules, modulation of extracellular matrix, influencing the levels of other cytokines and interactions with transcription factors. Furthermore, macrophages are among the first haematopoietic cells to be found in the kidney and other embryonic tissues. Their numbers and activation status are closely regulated by cytokines and evidence is accumulating that as well as scavenging cellular debris, macrophages themselves may induce cell death during organogenesis. Disruption of any of these carefully regulated and interdependent processes may cause disease.