NERVE GROWTH-FACTOR AND AUTOIMMUNE RHEUMATIC DISEASES

Nerve growth factor (NGF) is the first discovered and best known neuro trophic factor and is required for the survival and differentiation of a variety of neuronal cell types in both the peripheral and central n ervous system. Recent studies indicate that NGF is synthesized by cell s of immune system, lineage and that its level increases during inflam matory responses, while cytokines such as interleukin-1beta and tumor necrosis factor-alpha are potent inducers of NGF secretion. The role p layed by NGF on cells of the immune system was strengthened by recent evidence demonstrating that cells normally present in inflammatory tis sues, such as mast cells and lymphocytes, express NGF receptors and ar e receptive to the action of NGF. Studies carried out in our and other laboratories showed that NGF is expressed in the synovial fluid of pa tients 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 expr ess the human tumor necrosis factor-gene also showed elevated levels o f NGF. Significant increases in NGF levels have been found in the sera of patients with systemic lupus erythematosus and in the dermis of pa tients affected by systemic sclerosis. In this paper the hypothesis th at NGF is involved in the pathophysiology of autoimmune rheumatic arth ritis is discussed.