Nerve Growth Factor in Rheumatic Diseases

Objectives: The nervous system modulates the immune response in many autoimmune syndromes by neurogenic inflammation. One of the pivotal mediators is nerve growth factor (NGF), which is known for its effects on neuronal survival and growth. There is considerable evidence that NGF acts as an important mediator of many immune responses. This article reviews the role of NGF in rheumatic diseases and strategies for potential therapeutic interventions. Methods: We conducted a database search using Medline and Medpilot. Eight hundred abstracts containing the keyword NGF and 1 of the following terms were reviewed: arthritis, neurogenic inflammation, rheumatoid arthritis, osteoarthritis, collagen arthritis, arteritis, psoriasis, psoriatic arthritis, Sjogren syndrome, systemic lupus erythematosus, gout, osteoporosis, lower back pain, lumbar disc herniation, nerve root compression, spondyloarthritis, spondylarthropathy, algoneurodystrophy, fibromyalgia, Kawasaki syndrome, polyarteritis nodosa, cytokine, vasculitis, pain, therapy, and antagonist. Articles were analyzed based on relevance and content. Most clinical trials and studies with human specimens were included. Studies with experimental animal models were selected if they contained relevant data. Results: NGF is overexpressed in many inflammatory and degenerative rheumatic diseases. Concentrations differ to some extent and sometimes even show contradictory results. NGF is found in serum, synovial fluid, and cerebrospinal fluid, and tissue specimens. NGF concentrations can be correlated with the extent of inflammation and/or clinical activity in many conditions. In rheumatoid arthritis, NGF levels are significantly higher as compared with osteoarthritis. Conclusions: NGF is a significant mediator and modulator of inflammation. NGF sometimes shows detrimental and sometimes regenerative activity. These findings indicate potential therapeutic interventions using either NGF antagonists or recombinant NGF. (C) 2010 Published by Elsevier Inc. Semin Arthritis Rheum 40:109-126