Leukaemia inhibitory factor is required for normal inflammatory responses to injury in the peripheral and central nervous systems in vivo and is chemotactic for macrophages in vitro

The cytokine leukaemia inhibitory factor (LIF) is up-regulated in glial cel ls after injury to the peripheral and central nervous systems. In addition, LIF is required for the changes in neuropeptide expression that normally o ccur when the axons of sympathetic and sensory neurons are transected. We i nvestigated whether LIF is also necessary for the initial inflammatory resp onse that follows mechanical injury to the sciatic nerve and cerebral corte x of adult mice. We find that inflammatory cell infiltration into crushed s ciatic nerve is significantly slower in LIF knock-out (KO) mice compared wi th wild-type (WT) mice. Similarly, the microglial and astroglial responses to surgical injury of the cortex are significantly slower in LIF KO mice co mpared with WT mice. Consistent with these in vivo results, LIF is chemotac tic for peritoneal macrophages in a microchamber culture assay. Thus, LIF i s a key regulator of neural injury in vivo, where it is produced by glia an d can act directly on neurons, glia and inflammatory cells. We also find th at the initial inflammatory response to cortical injury is diminished in in terleukin (IL)-6 KO mice. Surprisingly, however, the inflammatory response in LIF-IL-6 double KO mice is very similar to that of the single KO mice, s uggesting that these cytokines may act in series rather than in parallel in this response.