Nerve growth factor and substance P are useful plasma markers of disease activity in atopic dermatitis

Background Neurogenic components, such as neurotrophic factors and neuropeptides, are probably involved in the pathogenesis of atopic dermatitis (AD) via the neuroimmunocutaneous system. Numerous in vitro and in vivo studies have shown that nerve growth factor (NGF), the best-characterized member of the neurotrophin family, modulates the synthesis of the neuropeptide substance P (SP), both of which may be associated with the pathogenesis of human allergic diseases. Objectives To evaluate the levels of NGF and SP in the plasma of patients with AD and to examine their possible correlation with disease activity. Methods We measured plasma levels of NGF by an immunoenzymatic assay and of SP by aradioimmunoassay in 52 patients with AD, and compared them with 35 normal non-atopic controls. The severity of the disease in AD patients was evaluated using validated clinical scoring systems. Results Patients with AD had significant increases in plasma levels of NGF and SP compared with controls (P < 0.0005 and P < 0.0001, respectively). A positive correlation between the plasma levels of NGF and SP was found in AD patients (correlation coefficient, Cc = 0.920, P < 0.0001). There was a significant correlation of plasma NGF and SP levels with disease activity evaluated using three different scoring systems: the grading system of Rajka and Langeland (P < 0.001 and P < 0.01, respectively), the objective Severity Scoring of AD (Cc = 0.656, P < 0.005 and Cc = 0.752, P < 0.0005, respectively) and the Eczema Area and Severity Index (Cc = 0.740, P < 0.001 and Cc = 0.765, P < 0.005, respectively). Conclusions These data represent the first reported evidence of increased plasma levels of NGF and SP in an allergic human skin disease. They suggest that these neurogenic factors systemically modulate the allergic response in AD, probably through interactions with cells of the immune-inflammatory component. In addition, NGF and SP may be useful markers of disease activity in patients with AD.