LEUKEMIA INHIBITORY FACTOR INDUCES SYMPATHETIC SPROUTING IN INFECT DORSAL-ROOT GANGLIA IN THE ADULT-RAT IN-VIVO

1. The role of the cytokine leukemia inhibitory factor (LIF) in axotom y-induced sprouting of postganglionic sympathetic fibres into the dors al root ganglia was examined in the adult rat. 2. Immunocytochemistry was used to study the distribution and density of tyrosine hydroxylase -immunoreactive (TH-IR) fibres within the lumbar dorsal root ganglia a nd lumbar spinal nerves 14 days following continuous intrathecal infus ion of LIF (0.33 mg ml(-1)), or 14 days following unilateral periphera l nerve axotomy. 3. In LIF-treated animals, numerous pericellular TH-I R basket-like structures were observed surrounding sensory neurones, w hich were absent from controls. 4. The number of TH-IR fibres within t he L3, L4 and L5 spinal nerves was significantly higher in LIF-treated animals than in control or saline-treated animals (P < 0.01, Student' s t test). 5. Unilateral ligation of the L4 spinal nerve or unilateral sciatic nerve ligation was also associated with the formation of TH-I R baskets around sensory neurones and a significant increase in the nu mber of TH-IR fibres within the lumbar spinal nerves (P < 0.01, Studen t's t test). 6. The percentage of neurones surrounded by TH-IR baskets within the L3 and L4 dorsal root ganglia following sciatic axotomy wa s significantly reduced in animals treated continuously for 2 weeks wi th a monoclonal antibody against the LIF receptor motif, gp130 (0.833 mg ml(-1)) (P < 0.05, Mann-Whitney U test). Antibody treatment did not reduce the axotomy-induced increase in TH-IR fibres within lumbar spi nal nerves. 7. These results demonstrate that exogenous application of the axotomy-associated cytokine LIP is associated with sprouting of u ninjured postganglionic sympathetic neurones around sensory neurones w ithin the dorsal root ganglion. It is likely that increased LIF expres sion following peripheral axotomy plays an important role in the novel sympathetic sprouting observed within sensory ganglia following perip heral nerve injury.