Nickel ingested with food can elicit either systemic cutaneous or 
gastrointestinal symptoms causing a systemic nickel allergy syndrome (SNAS) that 
can be treated with tolerance by oral ingestion of the metal. It has been 
suggested that interleukins 2 (IL-2) and 10 (IL-10) are involved in the 
mechanisms underlying oral tolerance. We evaluated the clinical efficacy of oral 
desensitization therapy in SNAS consisting in the administration of nickel 
sulphate. Because nickel allergy prevalently affects women, only female subjects 
(N = 22) were recruited. Oral nickel desensitizing therapy was associated with 
low-nickel diet for three months. Before and after therapy, clinical conditions 
were evaluated, and circulating cytokines IL-2 and IL-10 were measured. After 
the two-year treatment, visual analogue scale (VAS) scores for symptoms were 
significantly reduced (P less than 0.001). Patients were released by either 
cutaneous or gastrointestinal symptoms and by tolerating nickel-containing food. 
At the end of the treatment, nickel oral challenge test was negative in 18 
patients, and IL-2 level in the serum was significantly reduced while IL-10 was 
increased, although this datum was not statistically significant. Our study 
confirms the clinical efficacy of nickel oral immunotherapy and focuses on the 
mechanisms triggered by oral tolerance indicating that reduction of IL-2 can be 
associated with success of oral nickel desensitizing therapy.