Nickel-induced cytokine production from mononuclear cells in nickel-sensitive individuals and controls. Cytokine profiles in nickel-sensitive individuals with nickel allergy-related hand eczema before and after nickel challenge.
Exposure to nickel is a major cause of allergic contact dermatitis which is considered to be an inflammatory response induced by antigen-specific T cells. Here we describe the in vitro analysis of the nickel-specific T-cell-derived cytokine response of peripheral blood mononuclear cells from 35 nickel-allergic and 30 non-nickel-allergic individuals. Peripheral blood mononuclear cells were stimulated with 10(-4) and 10(-5) mol/l NiSO4 for 6 days and then additionally with ionomycin and phorbol myristate acetate for 24 h. Culture supernatants were analysed for interleukin-4 (IL-4), IL-5, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) by quantitative ELISA. The analysis showed that the synthesis of IL-4 and IL-5 but not of IFN-gamma or TNF-alpha was significantly higher in the nickel-allergic individuals. The finding of preferential synthesis of Th2 cytokines was somewhat of a surprise, since previous studies have suggested a Th1 response in nickel-mediated allergic contact dermatitis. Subsequently, the nickel-allergic individuals were randomized to experimental exposure to nickel or vehicle in a double-blind design. A daily 10-min exposure of one finger to 10 ppm nickel solution for 1 week followed by 100 ppm for an additional week evoked a clinical response of hand eczema in the nickel-exposed group. Blood samples were drawn on days 7 and 14 after the start of this exposure to occupationally relevant concentrations of nickel. No statistically significant differences were observed in the nickel-induced in vitro cytokine response during the exposure period. Our results indicate the possibility that IL-4 and IL-5 are involved in the pathogenesis of nickel-mediated contact dermatitis.
Reference Laboratory, National Institute of Occupational Health, Copenhagen, Denmark. lbo@ami.dk
L
L
Borg
J M
JM
Christensen
J
J
Kristiansen
N H
NH
Nielsen
T
T
Menné
L K
LK
Poulsen
D016207:Cytokines / Q000032:analysis*; D017449:Dermatitis, Allergic Contact / Q000209:etiology / Q000276:immunology*; D009783:Dermatitis, Occupational / Q000209:etiology / Q000276:immunology*; D004311:Double-Blind Method; D006229:Hand Dermatoses / Q000209:etiology / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D015848:Interleukin-5 / Q000032:analysis; D015759:Ionomycin / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D009532:Nickel / Q000009:adverse effects / Q000276:immunology; D012882:Skin Tests; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D016207:Cytokines; D015848:Interleukin-5; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D015759:Ionomycin; D009532:Nickel; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate