Effect of Leukemia Inhibitory Factor in Experimental Cisplatin Neuropathy in Mice

Abstract

In this study, the effect of leukemia inhibitory factor (LIF) on cisplatin (CDDP)-induced neuropathy was evaluated. Mice were treated with CDDP, 2 mg/kg i.p. twice a week nine times. During the last week some of the mice were also injected with LIF, 2 mug/kg s.c. every other day for a total of four injections. Development of neuropathy was evaluated with changes in tail flick latency and sensory nerve conduction velocity (NCV). At the end of the treatment period dorsal root ganglia (DRG) were microscopically examined. Some of the DRGs were explanted into extracellular matrix, covered with culture medium and incubated for 3 days. During and at the end of the incubation, cellular migration and axonal outgrowth from the DRGs were quantified. LIF proved effective in reversing the increase in tail flick latency (p < 0.05) and improving the reduction in NCV induced by CDDP. CDDP led to smaller nuclear and somatic size in neurons, while with LIF, the latter was restored to control values (p<0.01). No apoptotic nucleus was observed among DRG neurons while very few and moderate numbers detected among satellite and Schwann cells, respectively. With LIF, none of the cells had apoptosis. CDDP caused a decrease in the number of migrating cells and in the length of outgrowing axons while LIF treatment restored both capacities (p < 0.05) In conclusion, in CDDP-induced neuropathy, LIF was found to be effective in correcting some functional and morphological deteriorations related with major involvement of Schwann cells. (C) 2004 Elsevier Ltd. All rights reserved.