An immunohistochemical study of increased tumor necrosis factor-α in the skin of patients with amyotrophic lateral sclerosis

Tumor necrosis factor-α (TNF-α) is a major inflammatory cytokine that elicits a wide range of biological responses and is implicated in the pathogenesis of neurodegenerative diseases. Skin studies from patients with amyotrophic lateral sclerosis (ALS) have shown unique pathological and biochemical abnormalities. The lack of bedsore formation is considered characteristic of ALS. We undertook a quantitative immunohistochemical study of TNF-α in the skin from patients with ALS and controls with other neurologic or muscular diseases. Immunohistochemistry for TNF-α demonstrated cytoplasmic activity in the epidermis and in some blood vessels and glands. The proportion of TNF-α-positive (TNF-α+) cells in the epidermis in patients with ALS was significantly higher (p < 0.001) than in controls. There was a significant positive relationship (r = 0.87, p < 0.001) between this proportion and duration of illness in patients with ALS, but there was no such relationship in control subjects. The optical density of TNF-α+ cells in the epidermis in patients with ALS was markedly higher (p < 0.001) than in controls. There was a significant positive relationship (r = 0.70, p < 0.001) between the immunoreactivity and duration of illness in patients with ALS. However, there was no such relationship in controls. In addition, there was an appreciable positive correlation (r = 0.59, p < 0.01) in patients with ALS between the proportion of TNF-α+ cells and the optical density of these cells, but with no correlation in controls. These data suggest that changes in TNF-α identified in the skin of patients with ALS are likely to be related to the disease process and that metabolic alterations of TNF-α may take place in the skin of patients with ALS.