Renal synthesis of leukaemia inhibitory factor (LIF), under normal and inflammatory conditions

Leukaemia inhibitory factor (LIF) is a pleiotropic cytokine that is particu larly involved in nephrogenesis and repair of the extracellular matrix, Tra nsgenic mice overexpressing LIF have mesangial proliferative glomerulonephr itis, Also, during local inflammatory reactions, such as kidney graft rejec tion or urinary tract infections, urinary LIF excretion is enhanced. The ai m of the study therefore was to study LIF production by normal and inflamma tory diseased kidneys (glomerulonephritis or graft rejection), maintained i n short cultures. To determine the responsibility of the kidney itself in L IF synthesis, we measured LIF secretion into the culture supernatants of hu man mesangial or renal tubular epithelial cells. Fragments from diseased ki dneys, whether grafts or not, released more LIF than normal human kidney fr agments, mesangial or renal tubular epithelial cells, However, LIF producti on was delayed in renal transplants compared to glomerulonephritic samples taken from untreated patients. In every case, LIF production was enhanced b y interleukin 1 beta (IL-1 beta) and inhibited by IL-4 or dexamethasone, ex cept in two severe rejection episodes. So, LIF appeared to respond to pro- and anti-inflammatory stimuli, in vitro and in vivo. Considering its biolog ical effects, LIF could play a role in inflammatory renal diseases. (C) 200 0 Academic Press.