Leukemia inhibitory factor induces sympathetic sprouting in intact dorsal root ganglia in the adult rat in vivo.

Abstract

1. The role of the cytokine leukemia inhibitory factor (LIF) in axotomy-induced sprouting of postganglionic sympathetic fibres into the dorsal 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 and lumbar spinal nerves 14 days following continuous intrathecal infusion of LIF (0.33 mg ml-1), or 14 days following unilateral peripheral nerve axotomy. 3. In LIF-treated animals, numerous pericellular TH-IR basket-like structures were observed surrounding sensory neurones, which were absent from controls. 4. The number of TH-IR fibres within the 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-IR baskets around sensory neurons and a significant increase in the number of TH-IR fibres within the lumbar spinal nerves (P < 0.01, Student's t test). 6. The percentage of neurones surrounded by TH-IR baskets within the L3 and L4 dorsal root ganglia following sciatic axotomy was significantly reduced in animals treated continuously for 2 weeks with 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 spinal nerves. 7. These results demonstrate that exogenous application of the axotomy-associated cytokine LIF is associated with sprouting of uninjured postganglionic sympathetic neurones around sensory neurones within the dorsal root ganglion. It is likely that increased LIF expression following peripheral axotomy plays an important role in the novel sympathetic sprouting observed within sensory ganglia following peripheral nerve injury.