Inflammatory mediators in human renal dysplasia

Background. Cytokines regulate many processes in the immune system and have recently been implicated in normal organogenesis. We previously demonstrat ed that the archetypal inflammatory cytokine tumour necrosis factor-alpha ( TNF-alpha) is expressed in the murine metanephros, and exogenous TNF-alpha inhibits nephrogenesis and increases macrophage numbers in vitro (Cale et a l., Int J Dev Biol 1998; 42: 663-674). The phenotype seen, with an arrest o f ureteric bud branching and failure of mesenchymal to epithelial conversio n, is similar to human renal dysplasia. Methods and results. In normal human fetal kidneys we demonstrated the pres ence of macrophages and T cells and also documented TNF receptor expression on ureteric bud derivatives. In contrast to normal tissues, TNF-alpha prot ein was detected in dysplastic kidneys. This factor was also detected in th e urine of fetuses with obstructive uropathy and TNF receptors were express ed in dysplastic tubules. Furthermore, we noted a fetal distribution of mac rophages and T cells in dysplastic tissues and persistent expression of the adhesion molecules neural cell adhesion molecule and intercellular adhesio n molecule. Conclusions. We suggest that abnormal expression of cytokines early in rena l development dysregulates normal patterns of adhesion molecule expression and inflammatory cells, and may contribute to the pathogenesis of renal dys plasia.