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.

Keywords: nerve growth factor, review, neurogenic inflammation, rheumatic diseases

Abbreviations: ACE, Angiotensin converting enzyme, BDNF, Brain-derived neurotrophic factor, CGRP, Calcitonin gene-related peptide, CNS, Central nervous system, CNTF, Ciliary neurotrophic factor, CRP, C-reactive protein, CSF, Cerebrospinal fluid, ECM, Extracellular matrix, ESR, Erythrocyte sedimentation rate, FMS, Fibromyalgia syndrome, GDNF, Glia cell line-derived neurotrophic factor, HB, Hemoglobin, IFN-γ, Interferon-γ, IL, Interleukin, IVD, Intervertebral discs, MC, Mast cell, NF-κB, Nuclear factor-κB, NGF, Nerve growth factor, MMP, Matrix metalloproteinase, NT, Neurotrophin, OA, Osteoarthritis, PNS, Peripheral nervous system, RA, Rheumatoid arthritis, RAS, Guanine-nucleotide binding protein, rh, Recombinant human, SF, Synovial fluid, SLE, Systemic lupus erythematosus, SP, Substance P, SSc, Progressive systemic sclerosis, TGF, Transforming growth factor, TNF, Tumor necrosis factor, Trk, Transmembrane tyrosine kinase