[Cytokines and peripheral neuropathies]

Abstract

Cytokines are polypeptides produced by various cells, with key-roles in regulation of immune response, inflammation and hematopoiesis. Cytokine-producing cells in peripheral nerve include resident and recruited macrophages, lymphocytes, and likely mastocytes, Schwann cells, and probably neurons. Cytokines are instrumental in pathogenesis of peripheral neuropathies during nerve lesions and tissue repair. Tumor necrosis factor-alpha (TNF-alpha) injection into nerve induces Wallerian degeneration. In contrast, interleukin-1 (IL-1) promotes detersion by scavenger macrophages, and increased synthesis of neurotrophic factor (nerve growth factor--NGF--and leukemia inhibitory factor--LIF). Neurotrophic cytokines IL-6, LIF and transforming growth factor-beta 1 (TGF-beta 1) are overexpressed in nerve after experimental axotomy and promote axonal growth until axon/Schwann cell contact. In the course of inflammatory demyelinating neuropathies, proinflammatory cytokines induce vascular permeability and breakdown of blood nerve barrier (TNF-alpha, vascular endothelial growth factor/vascular permeability factor--VEGF/VPF), favor leukocyte transmigration 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, the inflammatory process is likely favored by downregulation of the anti-inflammatory cytokine TGF-beta 1.