Neurotrophins and cytokines--intermediaries between the immune and nervous systems

Neurotrophins (NTs), including nerve growth factor (NGF), are multifunctional: in addition to their well-characterized neurotrophic functions they are known to regulate and to be regulated by cytokines, components of the immune system. In line with this we have found expression of a functional trk proto-oncogene, constituting the signal transducing-receptor for NGF, on monocytes/macrophages, lymphocytes and basophils. Moreover, NGF synthesis is regulated by a cytokine cascade including inflammatory mediators such as interleukin-1 and tumor necrosis factor-alpha. The fact that NGF levels are markedly elevated in cerebrospinal fluid of patients with multiple sclerosis and in serum of patients with systemic lupus erythematosus strongly indicates a role for NGF in immunopathology as well as in normal immune function.