Nerve growth factor and autoimmune rheumatic diseases.

Nerve growth factor (NGF) is the first discovered and best known neurotrophic factor and is required for the survival and differentiation of a variety of neuronal cell types in both the peripheral and central nervous system. Recent studies indicate that NGF is synthesized by cells of immune system lineage and that its level increases during inflammatory responses, while cytokines such as interleukin-1 beta and tumor necrosis factor-alpha are potent inducers of NGF secretion. The role played by NGF on cells of the immune system was strengthened by recent evidence demonstrating that cells normally present in inflammatory tissues, such as mast cells and lymphocytes, express NGF receptors and are receptive to the action of NGF. Studies carried out in our and other laboratories showed that NGF is expressed in the synovial fluid of patients with rheumatoid arthritis and other forms of chronic arthritis, as well as in the synovium of pharmacologically-induced arthritis in animal models. Moreover, arthritic transgenic mice which carry and express the human tumor necrosis factor-gene also showed elevated levels of NGF. Significant increases in NGF levels have been found in the sera of patients with systemic lupus erythematosus and in the dermis of patients affected by systemic sclerosis. In this paper the hypothesis that NGF is involved in the pathophysiology of autoimmune rheumatic arthritis is discussed.