" An increasing body of evidence indicates that the peripheral nervous system (PNS) is often affected in SSc,5 though it is not clearly understood whether the involvement represents a primary or a secondary event. None the less, PNS involvement is important in disease pathogenesis, because it has a pivotal role in the dysregulation of vascular tone, which is one of the main features, in particular in the earliest phase, of the disease.
Data generated in the past two decades have defined the properties and characteristics of nerve growth factor (NGF). NGF is a neurotrophic factor with a bioregulatory function on the nervous system and morphogenic, endoautoparacrine, and immunomodulatory functions. NGF seems to be synthesised by the peripheral terminals of the sympathetic and sensory neurons followed by NGF retrograde axonal transport.9 This mechanism can be blocked by capsaicin and antibodies specific to NGF.
In the skin, NGF is produced by fibroblasts, mast cells, lymphocytes, and keratinocytes. NGF may act as controller of cutaneous morphogenesis, pigmentation, wound healing, and inflammation. Indeed, in the PNS, NGF modulates the function of the nerve terminals, controlling their development, survival, and both the production and release of neurotransmitters. Increased amounts of NGF have been found in several autoimmune diseases. Moreover,NGF levels correlate with disease activity in vasculitides and in inflammatory joint diseases in adults and in children.
The conclusion clearly shows that NGF levels are increased in SSc and that the highest levels are found in the diffuse subset. Indeed, this work connects for the first time the increase of NGF circulating levels with lung disease and suggest a relation between NGF and neuropeptides. Further studies are needed to understand the relation between NGF and specific organ involvement, thus clarifying its role in the multifaceted pathogenesis of SSc."