Cytokines and peripheral nerve disorders

Peripheral nerve production of cytokines originates from resident and recruited macrophages, lymphocytes, mastocytes, Schwann cells, and probably neurons. Cytokines are involved in nerve lesions and repair. Tumor necrosis factor-alpha (TNF-alpha) injected into nerve induces Wallerian degeneration, whereas, interleukin-1 (IL-1) production promotes detersion by scavenger macrophages, and synthesis of neurotrophic factors (nerve growth factor-NGF- and leukemia inhibitory factor-LIF). After experimental axotomy, other neurotrophic factors, including IL-6, LIF and transforming growth factor-beta 1 (TGF-beta 1), are overexpressed in nerve and promote axonal growth until axon/Schwann cell contact. Proinflammatory cytokines are instrumental in the course of inflammatory demyelinating neuropathies. They increase vascular permeability and blood nerve barrier breakdown (TNF-alpha, vascular endothelial growth factor/ vascular permeability factor-VEGF/VPF), favor transmigration of leukocytes into nerve, induce activation and proliferation of lymphocytes (IL-1, IL-2) and macrophages (gamma-interferon-IFN-gamma), and have a direct myelinotoxic activity (TNF-alpha and TNF-beta). In addition, downregulation of the immunosuppressive cytokine TGF-beta 1 may favor the nerve inflammatory reactions.