Increase in NGF content and nerve fiber sprouting in human allergic contact eczema

There is increasing evidence for an intimate interaction of the skin and th e nervous system. As known from animal studies, nerve growth factor (NGF) i s essential for the innervation density and functional properties of sensor y neurons of the skin during embryogenesis and in adulthood, and possibly d uring cutaneous inflammation. This study examined NGF content and sprouting of nerves during the elicitation phase of contact allergy in human skin. S kin biopsies from patients (n=14) undergoing patch-testing were taken from positive test sites and control back skin 96 h after antigen application. N GF content was measured by enzyme-linked immuno-fluoresence assay. Immunohi stochemistry was performed for protein gene product 9.5 (PGP9.5), a marker that stains all neuronal elements, and growth-associated protein 43 (GAP43) , a marker for axonal growth cones. The NGF content was significantly incre ased in lesional skin in comparison with normal skin (4.2+/-0.6 pg to 2.9+/ -0.5 pg NGF per mg wet weight). The length of epidermal PGP9.5-immunoreacti ve (ir) fibers in lesional skin significantly increased from 3.4+/-0.9 mm i n normal skin to 5.3+/-1.0 mm in contact eczema, whereas dermal fibers were unaltered (11.1+/-2.7 mm vs 9.5+/-2.1 mm, respectively). GAP43-ir nerve en dings were significantly increased in both epidermis (1.6+/-0.3 mm to 2.6+/ -0.4 mm) and dermis (0.5+/-0.1 mm to 1.8+/-0.2 mm) in contact ecze ma. Thus , we have provided evidence for an NGF-mediated nerve-fiber sprouting in hu man contact eczema. This may have a functional impact on skin-associated im mune cells, in particular mast cells and Langerhans cells.